The Experts below are selected from a list of 10653 Experts worldwide ranked by ideXlab platform
Roel Vermeulen - One of the best experts on this subject based on the ideXlab platform.
-
a quantitative meta analysis of the relation between occupational Benzene Exposure and biomarkers of cytogenetic damage
Environmental Health Perspectives, 2020Co-Authors: Qing Lan, Bernice Scholten, Jelle Vlaanderen, Rob Stierum, Lutzen Portengen, Nat Rothman, Anjoeka Pronk, Roel VermeulenAbstract:BACKGROUND: The genotoxicity of Benzene has been investigated in dozens of biomonitoring studies, mainly by studying (classical) chromosomal aberrations (CAs) or micronuclei (MN) as markers of DNA damage. Both have been shown to be predictive of future cancer risk in cohort studies and could, therefore, potentially be used for risk assessment of genotoxicity-mediated cancers. OBJECTIVES: We sought to estimate an Exposure-response curve (ERC) and quantify between-study heterogeneity using all available quantitative evidence on the cytogenetic effects of Benzene Exposure on CAs and MN respectively. METHODS: We carried out a systematic literature review and summarized all available data of sufficient quality using meta-analyses. We assessed the heterogeneity in slope estimates between studies and conducted additional sensitivity analyses to assess how various study characteristics impacted the estimated ERC. RESULTS: Sixteen CA (1,356 individuals) and formula presented studies (2,097 individuals) were found to be eligible for inclusion in a meta-analysis. Studies where Benzene was the primary genotoxic Exposure and that had adequate assessment of both Exposure and outcomes were used for the primary analysis. Estimated slope estimates were an increase of 0.27% CA [(95% CI: 0.08%, 0.47%); based on the results from 4 studies] and 0.27% MN [(95% CI: formula presented , 0.76%); based on the results from 7 studies] per parts-per-million Benzene Exposure. We observed considerable between-study heterogeneity for both end points (formula presented ). DISCUSSION: Our study provides a systematic, transparent, and quantitative summary of the literature describing the strong association between Benzene Exposure and accepted markers of genotoxicity in humans. The derived consensus slope can be used as a best estimate of the quantitative relationship between real-life Benzene Exposure and genetic damage in future risk assessment. We also quantitate the large between-study heterogeneity that exists in this literature, a factor which is crucial for the interpretation of single-study or consensus slopes.
-
Benzene Exposure response and risk of myeloid neoplasms in chinese workers a multicenter case cohort study
Journal of the National Cancer Institute, 2019Co-Authors: Martha S Linet, Roel Vermeulen, Songnian Yin, Qing Lan, Lutzen Portengen, Ethel S Gilbert, Graca M Dores, Richard B Hayes, Nathaniel RothmanAbstract:BACKGROUND There is international consensus that Benzene Exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the Exposure response, particularly risks by time since Exposure and age at Exposure. METHODS In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). We estimated Benzene Exposures using hierarchical modeling of occupational factors calibrated with historical routine measurements, and evaluated Exposure response for cumulative Exposure and average intensity using Cox regression; P values were two-sided. RESULTS Increased MDS/AML risk with increasing cumulative Exposure in our a priori defined time window (2 to <10 years) before the time at risk was suggested (Ptrend = 08). For first Exposure (within the 2 to <10-year window) before age 30 years, the Exposure response was stronger (P = .004) with rate ratios of 1.12 (95% confidence interval [CI] = 0.27 to 4.29), 5.58 (95% CI = 1.65 to 19.68), and 4.50 (95% CI = 1.22 to 16.68) for cumulative Exposures of more than 0 to less than 40, 40 to less than 100, and at least 100 ppm-years, respectively, compared with no Exposure. There was little evidence of Exposure response after at least 10 years (Ptrend = .94), regardless of age at first Exposure. Average intensity results were generally similar. The risk for chronic myeloid leukemia was increased in exposed vs unexposed workers, but appeared to increase and then decrease with increasing Exposure. CONCLUSION For myeloid neoplasms, the strongest effects were apparent for MDS/AML arising within 10 years of Benzene Exposure and for first Exposure in the 2 to less than 10-year window before age 30 years.
-
identification of gene expression predictors of occupational Benzene Exposure
PLOS ONE, 2018Co-Authors: Courtney Schiffman, Min Shen, Luoping Zhang, Roel Vermeulen, Songnian Yin, Cliona M Mchale, Alan Hubbard, Stephen M Rappaport, Reuben Thomas, Qing LanAbstract:Background Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational Exposure to a range of Benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives In the current study, we sought to identify gene expression biomarkers predictive of Benzene Exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to Benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm Benzene Exposure, in 44 subjects with a mean air Benzene level of 0.55±0.248 ppm (minimum 0.203ppm). Results nCounter and microarray expression levels were highly correlated (coefficients >0.7, p 0.9 (p<0.0001) and were not predictive of other Exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Conclusions Using nCounter and SL, we validated the altered expression of multiple mRNAs by Benzene and identified gene pairs predictive of Exposure to Benzene at levels below the US occupational standard of 1ppm.
-
adductomic signatures of Benzene Exposure provide insights into cancer induction
Carcinogenesis, 2018Co-Authors: Hasmik Grigoryan, Luoping Zhang, Roel Vermeulen, Songnian Yin, Qing Lan, Nathaniel Rothman, Martyn T Smith, William M B Edmands, Henrik Carlsson, Stephen M RappaportAbstract:Although Benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is Benzene metabolism, which produces many reactive intermediates, some specific to Benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational Exposure to Benzene (exposed: 3.2-88.9 ppm, controls: 0.002-0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin, a nucleophilic hotspot in extracellular fluids. Of the 47 measured human serum albumin modifications, 39 were present at higher concentrations in Benzene-exposed workers than in controls and many of the exposed-control differences were statistically significant. Correlation analysis identified three prominent clusters of adducts, namely putative modifications by Benzene oxide and a Benzene diolepoxide that grouped with other measures of Benzene Exposure, adducts of reactive oxygen and carbonyl species, and Cys34 disulfides of small thiols that are formed following oxidation of Cys34. Benzene diolepoxides are potent mutagens and carcinogens that have received little attention as potential causes of human leukemia. Reactive oxygen and carbonyl species-generated by redox processes involving polyphenolic Benzene metabolites and by Cyp2E1 regulation following Benzene Exposure-can modify DNA and proteins in ways that contribute to cancer. The fact that these diverse human serum albumin modifications differed between Benzene-exposed and control workers suggests that Benzene can increase leukemia risks via multiple pathways involving a constellation of reactive molecules.
-
evaluating Exposure response associations for non hodgkin lymphoma with varying methods of assigning cumulative Benzene Exposure in the shanghai women s health study
Annals of Work Exposures and Health, 2017Co-Authors: Melissa C Friesen, Roel Vermeulen, Bryan A Bassig, Xiaoou Shu, Mark P Purdue, Patricia A Stewart, Yongbing Xiang, Wong Ho Chow, Gong Yang, Martha S LinetAbstract:Objectives To provide insight into the contributions of Exposure measurements to job Exposure matrices (JEMs), we examined the robustness of an association between occupational Benzene Exposure and non-Hodgkin lymphoma (NHL) to varying Exposure assessment methods. Methods NHL risk was examined in a prospective population-based cohort of 73087 women in Shanghai. A mixed-effects model that combined a Benzene JEM with >60000 short-term, area Benzene inspection measurements was used to derive two sets of measurement-based Benzene estimates: 'job/industry-specific' estimates (our presumed best approach) were derived from the model's fixed effects (year, JEM intensity rating) and random effects (occupation, industry); 'calibrated JEM' estimates were derived using only the fixed effects. 'Uncalibrated JEM' (using the ordinal JEM ratings) and Exposure duration estimates were also calculated. Cumulative Exposure for each subject was calculated for each approach based on varying Exposure definitions defined using the JEM's probability ratings. We examined the agreement between the cumulative metrics and evaluated changes in the Benzene-NHL associations. Results For our primary Exposure definition, the job/industry-specific estimates were moderately to highly correlated with all other approaches (Pearson correlation 0.61-0.89; Spearman correlation > 0.99). All these metrics resulted in statistically significant Exposure-response associations for NHL, with negligible gain in model fit from using measurement-based estimates. Using more sensitive or specific Exposure definitions resulted in elevated but non-significant associations. Conclusions The robust associations observed here with varying Benzene assessment methods provide support for a Benzene-NHL association. While incorporating Exposure measurements did not improve model fit, the measurements allowed us to derive quantitative Exposure-response curves.
Qing Lan - One of the best experts on this subject based on the ideXlab platform.
-
a quantitative meta analysis of the relation between occupational Benzene Exposure and biomarkers of cytogenetic damage
Environmental Health Perspectives, 2020Co-Authors: Qing Lan, Bernice Scholten, Jelle Vlaanderen, Rob Stierum, Lutzen Portengen, Nat Rothman, Anjoeka Pronk, Roel VermeulenAbstract:BACKGROUND: The genotoxicity of Benzene has been investigated in dozens of biomonitoring studies, mainly by studying (classical) chromosomal aberrations (CAs) or micronuclei (MN) as markers of DNA damage. Both have been shown to be predictive of future cancer risk in cohort studies and could, therefore, potentially be used for risk assessment of genotoxicity-mediated cancers. OBJECTIVES: We sought to estimate an Exposure-response curve (ERC) and quantify between-study heterogeneity using all available quantitative evidence on the cytogenetic effects of Benzene Exposure on CAs and MN respectively. METHODS: We carried out a systematic literature review and summarized all available data of sufficient quality using meta-analyses. We assessed the heterogeneity in slope estimates between studies and conducted additional sensitivity analyses to assess how various study characteristics impacted the estimated ERC. RESULTS: Sixteen CA (1,356 individuals) and formula presented studies (2,097 individuals) were found to be eligible for inclusion in a meta-analysis. Studies where Benzene was the primary genotoxic Exposure and that had adequate assessment of both Exposure and outcomes were used for the primary analysis. Estimated slope estimates were an increase of 0.27% CA [(95% CI: 0.08%, 0.47%); based on the results from 4 studies] and 0.27% MN [(95% CI: formula presented , 0.76%); based on the results from 7 studies] per parts-per-million Benzene Exposure. We observed considerable between-study heterogeneity for both end points (formula presented ). DISCUSSION: Our study provides a systematic, transparent, and quantitative summary of the literature describing the strong association between Benzene Exposure and accepted markers of genotoxicity in humans. The derived consensus slope can be used as a best estimate of the quantitative relationship between real-life Benzene Exposure and genetic damage in future risk assessment. We also quantitate the large between-study heterogeneity that exists in this literature, a factor which is crucial for the interpretation of single-study or consensus slopes.
-
Benzene Exposure response and risk of lymphoid neoplasms in chinese workers a multicenter case cohort study
American Journal of Industrial Medicine, 2020Co-Authors: Martha S Linet, Songnian Yin, Qing Lan, Lutzen Portengen, Ethel S Gilbert, Rudolf Vermeulen, Graca M Dores, Richard B Hayes, Nathaniel RothmanAbstract:BACKGROUND While international agreement supports a causal relationship of Benzene Exposure with acute myeloid leukemia, there is debate about Benzene and lymphoid neoplasm risks. METHODS In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated Benzene Exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated Benzene Exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative Exposure-response using Cox regression. RESULTS NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of Exposure-response for NHL or other specified LN. Based on a linear Exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative Benzene Exposure using a 2-year lag (Exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant Exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first Exposure, attained age, or time since Exposure. CONCLUSION Given the study strengths and limitations, we found little evidence of Exposure-response for Benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.
-
Benzene Exposure response and risk of myeloid neoplasms in chinese workers a multicenter case cohort study
Journal of the National Cancer Institute, 2019Co-Authors: Martha S Linet, Roel Vermeulen, Songnian Yin, Qing Lan, Lutzen Portengen, Ethel S Gilbert, Graca M Dores, Richard B Hayes, Nathaniel RothmanAbstract:BACKGROUND There is international consensus that Benzene Exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the Exposure response, particularly risks by time since Exposure and age at Exposure. METHODS In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). We estimated Benzene Exposures using hierarchical modeling of occupational factors calibrated with historical routine measurements, and evaluated Exposure response for cumulative Exposure and average intensity using Cox regression; P values were two-sided. RESULTS Increased MDS/AML risk with increasing cumulative Exposure in our a priori defined time window (2 to <10 years) before the time at risk was suggested (Ptrend = 08). For first Exposure (within the 2 to <10-year window) before age 30 years, the Exposure response was stronger (P = .004) with rate ratios of 1.12 (95% confidence interval [CI] = 0.27 to 4.29), 5.58 (95% CI = 1.65 to 19.68), and 4.50 (95% CI = 1.22 to 16.68) for cumulative Exposures of more than 0 to less than 40, 40 to less than 100, and at least 100 ppm-years, respectively, compared with no Exposure. There was little evidence of Exposure response after at least 10 years (Ptrend = .94), regardless of age at first Exposure. Average intensity results were generally similar. The risk for chronic myeloid leukemia was increased in exposed vs unexposed workers, but appeared to increase and then decrease with increasing Exposure. CONCLUSION For myeloid neoplasms, the strongest effects were apparent for MDS/AML arising within 10 years of Benzene Exposure and for first Exposure in the 2 to less than 10-year window before age 30 years.
-
identification of gene expression predictors of occupational Benzene Exposure
PLOS ONE, 2018Co-Authors: Courtney Schiffman, Min Shen, Luoping Zhang, Roel Vermeulen, Songnian Yin, Cliona M Mchale, Alan Hubbard, Stephen M Rappaport, Reuben Thomas, Qing LanAbstract:Background Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational Exposure to a range of Benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives In the current study, we sought to identify gene expression biomarkers predictive of Benzene Exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to Benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm Benzene Exposure, in 44 subjects with a mean air Benzene level of 0.55±0.248 ppm (minimum 0.203ppm). Results nCounter and microarray expression levels were highly correlated (coefficients >0.7, p 0.9 (p<0.0001) and were not predictive of other Exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Conclusions Using nCounter and SL, we validated the altered expression of multiple mRNAs by Benzene and identified gene pairs predictive of Exposure to Benzene at levels below the US occupational standard of 1ppm.
-
adductomic signatures of Benzene Exposure provide insights into cancer induction
Carcinogenesis, 2018Co-Authors: Hasmik Grigoryan, Luoping Zhang, Roel Vermeulen, Songnian Yin, Qing Lan, Nathaniel Rothman, Martyn T Smith, William M B Edmands, Henrik Carlsson, Stephen M RappaportAbstract:Although Benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is Benzene metabolism, which produces many reactive intermediates, some specific to Benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational Exposure to Benzene (exposed: 3.2-88.9 ppm, controls: 0.002-0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin, a nucleophilic hotspot in extracellular fluids. Of the 47 measured human serum albumin modifications, 39 were present at higher concentrations in Benzene-exposed workers than in controls and many of the exposed-control differences were statistically significant. Correlation analysis identified three prominent clusters of adducts, namely putative modifications by Benzene oxide and a Benzene diolepoxide that grouped with other measures of Benzene Exposure, adducts of reactive oxygen and carbonyl species, and Cys34 disulfides of small thiols that are formed following oxidation of Cys34. Benzene diolepoxides are potent mutagens and carcinogens that have received little attention as potential causes of human leukemia. Reactive oxygen and carbonyl species-generated by redox processes involving polyphenolic Benzene metabolites and by Cyp2E1 regulation following Benzene Exposure-can modify DNA and proteins in ways that contribute to cancer. The fact that these diverse human serum albumin modifications differed between Benzene-exposed and control workers suggests that Benzene can increase leukemia risks via multiple pathways involving a constellation of reactive molecules.
Nathaniel Rothman - One of the best experts on this subject based on the ideXlab platform.
-
Benzene Exposure response and risk of lymphoid neoplasms in chinese workers a multicenter case cohort study
American Journal of Industrial Medicine, 2020Co-Authors: Martha S Linet, Songnian Yin, Qing Lan, Lutzen Portengen, Ethel S Gilbert, Rudolf Vermeulen, Graca M Dores, Richard B Hayes, Nathaniel RothmanAbstract:BACKGROUND While international agreement supports a causal relationship of Benzene Exposure with acute myeloid leukemia, there is debate about Benzene and lymphoid neoplasm risks. METHODS In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated Benzene Exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated Benzene Exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative Exposure-response using Cox regression. RESULTS NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of Exposure-response for NHL or other specified LN. Based on a linear Exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative Benzene Exposure using a 2-year lag (Exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant Exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first Exposure, attained age, or time since Exposure. CONCLUSION Given the study strengths and limitations, we found little evidence of Exposure-response for Benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.
-
Benzene Exposure response and risk of myeloid neoplasms in chinese workers a multicenter case cohort study
Journal of the National Cancer Institute, 2019Co-Authors: Martha S Linet, Roel Vermeulen, Songnian Yin, Qing Lan, Lutzen Portengen, Ethel S Gilbert, Graca M Dores, Richard B Hayes, Nathaniel RothmanAbstract:BACKGROUND There is international consensus that Benzene Exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the Exposure response, particularly risks by time since Exposure and age at Exposure. METHODS In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). We estimated Benzene Exposures using hierarchical modeling of occupational factors calibrated with historical routine measurements, and evaluated Exposure response for cumulative Exposure and average intensity using Cox regression; P values were two-sided. RESULTS Increased MDS/AML risk with increasing cumulative Exposure in our a priori defined time window (2 to <10 years) before the time at risk was suggested (Ptrend = 08). For first Exposure (within the 2 to <10-year window) before age 30 years, the Exposure response was stronger (P = .004) with rate ratios of 1.12 (95% confidence interval [CI] = 0.27 to 4.29), 5.58 (95% CI = 1.65 to 19.68), and 4.50 (95% CI = 1.22 to 16.68) for cumulative Exposures of more than 0 to less than 40, 40 to less than 100, and at least 100 ppm-years, respectively, compared with no Exposure. There was little evidence of Exposure response after at least 10 years (Ptrend = .94), regardless of age at first Exposure. Average intensity results were generally similar. The risk for chronic myeloid leukemia was increased in exposed vs unexposed workers, but appeared to increase and then decrease with increasing Exposure. CONCLUSION For myeloid neoplasms, the strongest effects were apparent for MDS/AML arising within 10 years of Benzene Exposure and for first Exposure in the 2 to less than 10-year window before age 30 years.
-
adductomic signatures of Benzene Exposure provide insights into cancer induction
Carcinogenesis, 2018Co-Authors: Hasmik Grigoryan, Luoping Zhang, Roel Vermeulen, Songnian Yin, Qing Lan, Nathaniel Rothman, Martyn T Smith, William M B Edmands, Henrik Carlsson, Stephen M RappaportAbstract:Although Benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is Benzene metabolism, which produces many reactive intermediates, some specific to Benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational Exposure to Benzene (exposed: 3.2-88.9 ppm, controls: 0.002-0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin, a nucleophilic hotspot in extracellular fluids. Of the 47 measured human serum albumin modifications, 39 were present at higher concentrations in Benzene-exposed workers than in controls and many of the exposed-control differences were statistically significant. Correlation analysis identified three prominent clusters of adducts, namely putative modifications by Benzene oxide and a Benzene diolepoxide that grouped with other measures of Benzene Exposure, adducts of reactive oxygen and carbonyl species, and Cys34 disulfides of small thiols that are formed following oxidation of Cys34. Benzene diolepoxides are potent mutagens and carcinogens that have received little attention as potential causes of human leukemia. Reactive oxygen and carbonyl species-generated by redox processes involving polyphenolic Benzene metabolites and by Cyp2E1 regulation following Benzene Exposure-can modify DNA and proteins in ways that contribute to cancer. The fact that these diverse human serum albumin modifications differed between Benzene-exposed and control workers suggests that Benzene can increase leukemia risks via multiple pathways involving a constellation of reactive molecules.
-
o08 2 occupational Exposure to Benzene and alterations in immune inflammatory markers
Occupational and Environmental Medicine, 2016Co-Authors: Nathaniel Rothman, Min Shen, Luoping Zhang, Roel Vermeulen, Songnian Yin, Stephen M Rappaport, Bryan A Bassig, Mark P Purdue, Troy J Kemp, Martha S LinetAbstract:Introduction Benzene is an occupational solvent that is used in multiple industries, and is a known human carcinogen (IARC Group 1) that is hematotoxic and causes acute myeloid leukaemia. Further, there is some evidence that occupational Benzene Exposure is associated with certain lymphoid neoplasms. To follow up these observations, we evaluated the relationship between occupational Benzene Exposure and levels of immune markers that were measured using a multiplex panel. Methods A Luminex bead-based assay was conducted among 52 factory workers exposed to Benzene and 31 unexposed workers that were enrolled in a cross-sectional molecular epidemiology study in China. Personal Benzene Exposure was repeatedly monitored in workers using a 3 M organic vapour passive monitoring badge before phlebotomy. Linear regression was used to evaluate differences in marker concentrations between Benzene exposed vs. unexposed workers, and to explore Exposure-response trends (unexposed, ≤5 ppm, >5 ppm). Results Multiple markers were significantly altered in Benzene exposed workers compared to unexposed workers (P-value Conclusions Occupational Exposure to Benzene was associated with a range of immune perturbations including alterations in markers that regulate B-cell chemotaxis and regulation of cytotoxic T-cell activity. Notably, two of these markers (TNF-α and BCA-1) have previously been associated with risk of non-Hodgkin lymphoma in prospective studies. These observations provide additional biologic insight into the effects of Benzene on the immune system.
-
Benzene Exposure and risk of lymphohaematopoietic cancers in 25 000 offshore oil industry workers
British Journal of Cancer, 2015Co-Authors: Jo Steinson Stenehjem, Qing Lan, Kristina Kjaerheim, Magne Bratveit, Sven Ove Samuelsen, Francesco Baroneadesi, Nathaniel Rothman, Tom Kristian GrimsrudAbstract:Benzene Exposure and risk of lymphohaematopoietic cancers in 25 000 offshore oil industry workers
Jamsai Suwansaksri - One of the best experts on this subject based on the ideXlab platform.
-
genotoxic monitoring and Benzene Exposure assessment of gasoline station workers in metropolitan bangkok sister chromatid exchange sce and urinary trans trans muconic acid t t ma
Asian Pacific Journal of Cancer Prevention, 2011Co-Authors: Tanasorn Tunsaringkarn, Jamsai Suwansaksri, Suphan Soogarun, Wattasit Siriwong, Anusorn Rungsiyothin, Kalaya Zapuang, Mark G RobsonAbstract:Early warning of the potential of mutagens or carcinogens caused by Benzene Exposure that might occur in gasoline station workers can be achieved by examining 2 major biomarkers: sister chromatid exchange (SCE) and trans, trans-muconic acid (t,t-MA), a urinary metabolite of Benzene. The main objective of this study was to assess Benzene Exposure and monitor the genotoxic effect of gasoline station workers in Bangkok, Thailand. Blood and urine samples were collected from 33 gasoline station workers, working in Pathumwan district area, central Bangkok, Thailand, for SCE and t,t-MA analysis, from April to June 2009. Control samples were collected from 30 office workers and students in the same area at the same period. Our results indicated significantly higher frequencies of SCE in gasoline exposed workers were than in controls (p<0.01), independent of gender. Urinary t,t-MA and t,t-MA/creatinine levels of gasoline exposed workers were also significantly higher than the control groups (p<0.05) were significantly higher in women than men workers (p<0.01). Calculated chromosomal damage relative risk (RR) of gasoline station workers was 3.00 (95% CI = 1.81 - 4.98, p<0.001) compared to controls. The gasoline exposed workers had potentially higher risk of chromosomal damage and cancer development because of direct contact to Benzene.
-
a correlative study on red blood cell parameters and urine trans trans muconic acid in subjects with occupational Benzene Exposure
Toxicologic Pathology, 2007Co-Authors: Viroj Wiwanitkit, Suphan Soogarun, Jamsai SuwansaksriAbstract:Benzene is of particular concern because of recent research indicating that Benzene Exposure can result in toxicity. The hematotoxic effect of Benzene is mentioned. However, there is little knowledge about the correlation between the biomarker of Benzene Exposure and changes in red blood cell parameters. Here, the correlation between the urine trans, trans-muconic acid (ttMA) level and red blood cell parameters were studied in 30 Thai subjects at risk. The regression analysis shows no significant correlation between urine ttMA and any studied red cell parameters (Hb, MCV or MCH). Based on our hematologic data, we proposed that only investigation for the urine ttMA might be not sufficient in detection of alteration in red blood cell parameters in the exposed population. Combinations between biomarker and hematological test are recommended.
-
a note on urine trans trans muconic acid level among a sample of thai police implication for an occupational health issue
Yale Journal of Biology and Medicine, 2003Co-Authors: Viroj Wiwanitkit, Jamsai Suwansaksri, Suphan SoogarunAbstract:Benzene Exposure is of particular concern because recent research indicating that Benzene Exposure can result in chronic toxicity, therefore, monitoring for Benzene Exposure among at-risk workers is recommended. In Exposure- and risk-evaluation, the monitoring of Benzene by peripheral biomarker has several advantages over technical assessment of Exposure. For this purpose, the urine trans, trans muconic acid (ttMA)e level is accepted as a useful monitoring tool for early diagnosis of dangerous Exposure. Apart from the industrial workers, there are other occupations with high risk for Benzene Exposure. In this study, we study another at-risk occupation, the police. Thirty-nine urine samples were obtained from 39 Thai police working close to traffic in an urban area. All 39 samples were analyzed for ttMA level and compared to 10 other controls. The average urine ttMA level for the control and exposed group were < 0.05 mg/gCr and was 0.79 +/- 1.43 mg/gCr, respectively. Significant higher urine ttMA acid level among the police were observed (p <.05). Working in the air pollution in the urban area can be health hazard for the police. Exposure to the Benzene from automobile exhaust can be an important occupational problem for these police.
-
urine trans trans muconic acid as a biomarker for Benzene Exposure in gas station attendants in bangkok thailand
Annals of Clinical and Laboratory Science, 2001Co-Authors: Viroj Wiwanitkit, Jamsai Suwansaksri, Paweena NasuanAbstract:The toxicity of Benzene, a chemical used in many industrial processes, involves bone marrow depression and leukemogenesis and is associated with damage to multiple classes of hematopoietic cells and hematopoietic functions. Environmental Exposure to Benzene causes an increased body burden, which is reflected in several biomarkers, eg, urine trans,trans-muconic acid (ttMA). Associated with the industrialization of Thailand, a developing country in Southeast Asia, workers in many occupations have acquired substantial risks of Benzene Exposure. In this study, Benzene Exposure was monitored by high-performance liquid chromatography (HPLC) of urine ttMA in 79 persons, including 49 controls and 30 gas station attendants. In controls, urine ttMA concentration averaged 0.12 (SD +/- 0.03) mg/g creatinine; in gas station attendants, urine ttMA concentration averaged 4.00 (SD +/- 12.49) mg/g creatinine (p < 0.05). Based on these findings, wider use of urine ttMA determination is recommended as a biomarker for occupational Exposure to Benzene.
-
feasibility of urinary trans trans muconic acid determination using high performance liquid chromatography for biological monitoring of Benzene Exposure
Journal of the Medical Association of Thailand Chotmaihet thangphaet, 2001Co-Authors: Jamsai Suwansaksri, Paweena NasuanAbstract:Benzene is an important carcinogenic substance used in many industrial processes. Inhalation of this substance can cause both acute and chronic toxicity. In this study, monitoring of Benzene Exposure by high-performance liquid chromatography (HPLC) for urine trans, trans-muconic acid (ttMA) determination was adapted. We described a new adapted sensitive and specific HPLC method. We mixed 0.5 mL of urine sample with 2 mL of Tris Buffer containing vanillic acid as internal standard (IS) and percolate this through a preconditioned ion-exchange column. After rinsing the column with phosphoric acid solution, acetate buffer, and deionized water, we eluated the analytes with 2 mL of an equivolume solution of 1.5 mol/L sodium chloride and methanol. Of this, 10 microliter was injected into the HPLC column. The mobile phase consisted of, per liter, 10 ml of acetic acid, 100 ml of methanol, and 5 mmol/L sodium acetate. The flow rate was started at 1.2 ml/min. The ttMA and IS were detected at 4.2 to 4.4 and 12.6-13.3 minutes, respectively. The lowest detection limit was 0.05 mg/L.
Luoping Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Benzene Exposure and non hodgkin lymphoma a systematic review and meta analysis of human studies
The Lancet Planetary Health, 2021Co-Authors: Iemaan Rana, Craig Steinmaus, Sarah Dahlberg, Luoping ZhangAbstract:Summary Background Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental Exposures to toxic chemicals. Although the ubiquitous pollutant Benzene is an established leukemogen, its potential to cause non-Hodgkin lymphoma has been widely debated. We aimed to examine the potential link between Benzene Exposure and risk of non-Hodgkin lymphoma in humans by evaluating a wide array of cohort and case-control studies using electronic systematic review. Methods We did a comprehensive systematic review and meta-analysis of all qualified human epidemiological studies that assessed the relationship between Benzene Exposure and non-Hodgkin lymphoma. We queried the PubMed and Embase databases for relevant articles published before June 5, 2019, and applied the SysRev platform for study selection. All peer-reviewed human cohort and case-control studies that reported non-Hodgkin lymphoma risk estimates specifically for Benzene Exposure were eligible for inclusion. Studies that calculated relative risks (RRs) for industries or job types without identifying those specifically exposed to Benzene, that combined non-Hodgkin lymphoma with other cancer types, or that reported many different solvent Exposures together were excluded. From each study, two investigators independently extracted information on the study design, location, years, sample size, participation rates, age, sex, sources of cases and controls, diagnosis, histological verification, Exposure assessment, results, adjustment, and statistical analysis, and subsequently assessed study quality. We calculated the meta-analysis relative risk (meta-RR) and CIs using the fixed effect and random effect models, as well as assessing publication bias. Findings Our search yielded 2481 articles. After screening and removal of duplicates, 20 case-control studies and eight cohort studies were included in our meta-analysis, which included a total of 9587 patients with non-Hodgkin lymphoma. We reported an increased meta-relative risk (meta-RR) of 33% in highly exposed groups, when data were available (meta-RR 1·33 [95% CI 1·13–1·57], n=28). The meta-RR rose to 1·51 (1·22–1·87, n=18) in the studies that provided results specifically for highly exposed individuals. In particular, we reported a doubling of this risk for diffuse large B-cell lymphoma, a major non-Hodgkin lymphoma subtype (1·67 [1·01–2·77]). We also detected increased risks for follicular lymphoma (1·47 [0·95–2·27]) and hairy cell leukaemia (1·77 [0·99–3·16]), though they were not statistically significant. Funnel plot, Egger's test (p=0·77) and Begg's test (p=0·98) did not show evidence of publication bias. We evaluated the major aspects of causal inference and found evidence to support all the Hill considerations for assigning causation. Interpretation Our findings suggest a causal link between Benzene Exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma. Funding National Institute of Environmental Health Sciences.
-
identification of gene expression predictors of occupational Benzene Exposure
PLOS ONE, 2018Co-Authors: Courtney Schiffman, Min Shen, Luoping Zhang, Roel Vermeulen, Songnian Yin, Cliona M Mchale, Alan Hubbard, Stephen M Rappaport, Reuben Thomas, Qing LanAbstract:Background Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational Exposure to a range of Benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives In the current study, we sought to identify gene expression biomarkers predictive of Benzene Exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to Benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm Benzene Exposure, in 44 subjects with a mean air Benzene level of 0.55±0.248 ppm (minimum 0.203ppm). Results nCounter and microarray expression levels were highly correlated (coefficients >0.7, p 0.9 (p<0.0001) and were not predictive of other Exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Conclusions Using nCounter and SL, we validated the altered expression of multiple mRNAs by Benzene and identified gene pairs predictive of Exposure to Benzene at levels below the US occupational standard of 1ppm.
-
adductomic signatures of Benzene Exposure provide insights into cancer induction
Carcinogenesis, 2018Co-Authors: Hasmik Grigoryan, Luoping Zhang, Roel Vermeulen, Songnian Yin, Qing Lan, Nathaniel Rothman, Martyn T Smith, William M B Edmands, Henrik Carlsson, Stephen M RappaportAbstract:Although Benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is Benzene metabolism, which produces many reactive intermediates, some specific to Benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational Exposure to Benzene (exposed: 3.2-88.9 ppm, controls: 0.002-0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin, a nucleophilic hotspot in extracellular fluids. Of the 47 measured human serum albumin modifications, 39 were present at higher concentrations in Benzene-exposed workers than in controls and many of the exposed-control differences were statistically significant. Correlation analysis identified three prominent clusters of adducts, namely putative modifications by Benzene oxide and a Benzene diolepoxide that grouped with other measures of Benzene Exposure, adducts of reactive oxygen and carbonyl species, and Cys34 disulfides of small thiols that are formed following oxidation of Cys34. Benzene diolepoxides are potent mutagens and carcinogens that have received little attention as potential causes of human leukemia. Reactive oxygen and carbonyl species-generated by redox processes involving polyphenolic Benzene metabolites and by Cyp2E1 regulation following Benzene Exposure-can modify DNA and proteins in ways that contribute to cancer. The fact that these diverse human serum albumin modifications differed between Benzene-exposed and control workers suggests that Benzene can increase leukemia risks via multiple pathways involving a constellation of reactive molecules.
-
o08 2 occupational Exposure to Benzene and alterations in immune inflammatory markers
Occupational and Environmental Medicine, 2016Co-Authors: Nathaniel Rothman, Min Shen, Luoping Zhang, Roel Vermeulen, Songnian Yin, Stephen M Rappaport, Bryan A Bassig, Mark P Purdue, Troy J Kemp, Martha S LinetAbstract:Introduction Benzene is an occupational solvent that is used in multiple industries, and is a known human carcinogen (IARC Group 1) that is hematotoxic and causes acute myeloid leukaemia. Further, there is some evidence that occupational Benzene Exposure is associated with certain lymphoid neoplasms. To follow up these observations, we evaluated the relationship between occupational Benzene Exposure and levels of immune markers that were measured using a multiplex panel. Methods A Luminex bead-based assay was conducted among 52 factory workers exposed to Benzene and 31 unexposed workers that were enrolled in a cross-sectional molecular epidemiology study in China. Personal Benzene Exposure was repeatedly monitored in workers using a 3 M organic vapour passive monitoring badge before phlebotomy. Linear regression was used to evaluate differences in marker concentrations between Benzene exposed vs. unexposed workers, and to explore Exposure-response trends (unexposed, ≤5 ppm, >5 ppm). Results Multiple markers were significantly altered in Benzene exposed workers compared to unexposed workers (P-value Conclusions Occupational Exposure to Benzene was associated with a range of immune perturbations including alterations in markers that regulate B-cell chemotaxis and regulation of cytotoxic T-cell activity. Notably, two of these markers (TNF-α and BCA-1) have previously been associated with risk of non-Hodgkin lymphoma in prospective studies. These observations provide additional biologic insight into the effects of Benzene on the immune system.
-
characterization of changes in gene expression and biochemical pathways at low levels of Benzene Exposure
PLOS ONE, 2014Co-Authors: Reuben Thomas, Luoping Zhang, Roel Vermeulen, Nathaniel Rothman, Cliona M Mchale, Alan Hubbard, Stephen M Rappaport, Kathryn Z Guyton, Jennifer Jinot, Babasaheb SonawaneAbstract:Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of Benzene Exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from 10 ppm) compared with 42 subjects with non-workplace ambient Exposure levels. Here, we further characterize these dose-dependent effects with continuous Benzene Exposure in all 125 study subjects. We estimated air Benzene Exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary Benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm Benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that Benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive Exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings.