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Adduct

The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform

Istvan Vincze – 1st expert on this subject based on the ideXlab platform

  • influence of cigarette smoking on the levels of dna Adducts in human bronchial epithelium and white blood cells
    International Journal of Cancer, 1990
    Co-Authors: David H Phillips, Bemadette Schoket, Alan Hewer, E Bailey, Szilard Kostic, Istvan Vincze

    Abstract:

    : The presence of carcinogen-DNA Adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA Adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5′-32P-labelled deoxyribonucleoside 3′,5′-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of Adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/- 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 Adducts/10(8) nucleotides, respectively. The differences in Adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between Adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P-post-labelling. Adduct levels in the smokers’ samples were not significantly different from levels in the non-smokers’ samples (2.53 +/- 1.31 and 2.12 +/- 1.44 Adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.

Bruce P Lanphear – 2nd expert on this subject based on the ideXlab platform

  • White blood cell DNA Adducts in a cohort of asthmatic children exposed to environmental tobacco smoke
    International Archives of Occupational and Environmental Health, 2011
    Co-Authors: Stephen E. Wilson, Glenn Talaska, Robert S. Kahn, Brenda Schumann, Jane Khoury, Anthony C. Leonard, Bruce P Lanphear

    Abstract:

    Purpose Exposure to environmental tobacco smoke (ETS) leads to molecular damage in the form of DNA Adducts. While lung cancer risk is higher among African Americans compared to White Americans, a few studies have tested for racial differences in DNA Adducts among children exposed to ETS. The purpose of this study was to test whether African American children have higher DNA Adducts levels compared to White children adjusted for ETS exposure. Methods Data and biologic specimens were drawn from an existing cohort of 212 asthmatic children. These subjects participated in a 12-month ETS-reduction trial that employed HEPA air cleaners with active filter cartridges and sham filter cartridges. White blood cell (WBC) DNA was analyzed for DNA Adducts using ^32P-postlabeling. We assessed ETS exposure using a validated air nicotine dosimeter. We determined the independent relationship between African American race and DNA Adduct levels adjusted for ETS exposure and air cleaner use. Results The mean age of the subjects was 8.4 years; 55% were African American. There was no difference in DNA Adduct levels between African American and White children (11.8 vs. 11.2 Adducts per 10^9 nucleotides, p  = 0.86), despite slightly higher levels of air nicotine exposure (3.4 vs. 2.2 μg/m^3, p  = 0.14). African American children used their air cleaners less often than White children. We found that the best predictor of DNA Adduct levels was the duration of air cleaner use ( r  = −0.133, p  = 0.056). This association was independent of cartridge type. Conclusions We did not see differences in Adduct levels by race even after accounting for the level of ETS exposure. However, there was a marginal inverse association between air cleaner use and Adducts. Additional research is required to understand this phenomenon.

Helmut Bartsch – 3rd expert on this subject based on the ideXlab platform

  • Modulation of benzo[a]pyrene diolepoxide-DNA Adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism
    Carcinogenesis, 2000
    Co-Authors: Margarita Rojas, Ingolf Cascorbi, Kroum Alexandrov, Erik Kriek, Guy Auburtin, Lucienne Mayer, Annette Kopp-schneider, Ivar Roots, Helmut Bartsch

    Abstract:

    The modulation of benzo[a]pyrene diolepoxide (BPDE)DNA Adduct levels by polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes was assessed in leukocytes of Caucasian males. Eighty-nine coke oven workers (35 smokers, 36 ex-smokers and 18 non-smokers) were recruited from job categories with different exposure levels to polycyclic aromatic hydrocarbons (PAH), together with 44 power plant workers tall smokers) not exposed to PAH, BPDE-DNA Adducts were detected in 69 of 133 (52%) DNA samples with a 100-fold variation (range 0.2-44 Adducts/10(8) nt) and a median of 1.6 Adducts/10(8) nt, All samples with the GSTM1 active genotype (n = 59) and five out of 74 samples with GSTM*0/*0 (7 %) showed nondetectable Adducts (0.2 Adducts/10(8) nt), The difference in Adduct level between the CSTM1*0/*0 and GSTM1 active genotypes was highly significant (P < 0.0001). No significant difference in Adduct level between the GSTT1*0/*0 and GSTT1 active genotypes was seen. All heterozygotes (CYP1A1*1/*2) from subjects of GSTM1 active type did not have detectable Adducts, Among the GSTM1-deficient individuals (n = 69), 42 with the CYP1A1*/*1 genotype showed a lower Adduct level (median 1.3, range 0.2-4.1 Adducts/10(8) nt) compared with 26 individuals with heterozygous mutated CYP1A1*/*2 genotypes (median 2.5, range 0.4-6.1 Adducts/10(8) nt, P < 0.015). One individual with low PAH exposure and the rare combination CYP1A1*2A/*2A-GSTM1*0/*0 showed an extremely high level of 44 Adducts/10(8) nt, Significant differences in detectable Adduct levels were found between the CYP1A1*1/*1 and CYP1A1*1/*2 genotypes in the exposed group low + medium (P = 0.01) and for all Adduct levels, detectable and non-detectable (set at a fixed value), in highly exposed individuals and in ex-smokers (P = 0.03), whereas no such differences were observed in the control group. Mutated CYP1A1*1/*2 increased the Adduct level in non-smokers from the exposed group (1.4 versus 2.2 Adducts/10(8) nt), but had no effect on the smokers from the exposed group (2.3 versus 2.8 Adducts/10(8) nt), When all variables were dichotomized, statistical evaluation showed that CYP1A1 status (P = 0.015), PAH exposure (P = 0.003) and smoking (P = 0.005) had significant effects on Adduct levels which increased in the order: CYP1A1*1/*1 < CYP1A1(*1/*2 or *2A/*2A); environmental exposure < occupational exposure; non-smokers < smokers, whereby Adducts increased with cigarette dose and the duration of smoking. Higher levels of BPDE-DNA Adducts in individuals with the combined CYP1A1(1/*2 or *2A/*2A)-GSTM1*0/*0 genotype suggest that these genotype combinations are at increased risk for contracting lung cancer when exposed to PAH.

  • Detection of carcinogen-DNA Adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin Adducts, and urinary mutagenicity.
    Cancer Epidemiology Biomarkers & Prevention, 1991
    Co-Authors: Glenn Talaska, Helmut Bartsch, Marlene Schamer, Paul L. Skipper, Steven R. Tannenbaum, Neil E. Caporaso, Leonard Unruh, Fred F. Kadlubar, Christian Malaveille, Paolo Vineis

    Abstract:

    The presence of covalent modifications in DNA obtained from exfoliated urothelial cells of smokers and nonsmokers was determined using 32P postlabeling methods. Urine and blood samples were procured from 73 persons. Cells were removed from the urine by filtration. DNA was isolated using an enzyme-solvent extraction method and then coprecipitated with glycogen. Sufficient DNA to detect 1 carcinogen-DNA Adduct/10(9) normal nucleotides was obtained from 40 of the 73 samples. DNA was hydrolyzed to 3′-phosphodeoxynucleotides and then 32P postlabeled under conditions of excess [32P]ATP. Carcinogen-DNA Adducts were resolved using anion-exchange thin-layer chromatography and visualized by autoradiography; film exposures lasted as long as 7 days. Twelve different carcinogen-DNA Adducts and a diagonal zone of radioactivity could be found, but no sample contained all Adducts. At least four Adducts appeared to be cigarette smoking related. These Adducts were from 2 to 20 times higher in the smokers than the nonsmokers. Two carcinogen-DNA Adducts were qualitatively very similar to Adducts described earlier in a study of human bladder biopsies. One of these corresponded to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. Adducts were correlated significantly with the levels of 4-aminobiphenyl hemoglobin Adducts and number of cigarettes smoked. In addition, levels of the putative N-(deoxyguanosin-8-yl)-4-aminobiphenyl Adduct and a measure of total Adducts were correlated with the mutagenic activity of the individual’s urine. These data suggest that noninvasive, biological monitoring techniques can be applied to the study of carcinogen-DNA Adducts in humans at high risk for bladder cancer.