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Nicolás Olea - One of the best experts on this subject based on the ideXlab platform.
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changes in the total effective Xenoestrogen burden texb of breast cancer patients during an 18 month post surgical follow up
Reproductive Toxicology, 2017Co-Authors: Juan P. Arrebola, Mariana F. Fernández, Nicolás Olea, Jose Pumarega, Miquel Porta, Josemanuel MolinamolinaAbstract:Abstract We aimed to assess changes in the total effective Xenoestrogen burden (TEXB) −a biomarker of combined effect of mixtures of Xenoestrogens- in breast cancer patients at surgery (breast adipose tissue) and at different time points during an 18-month follow-up (abdominal adipose tissue), and to analyze the potential influence of socio-demographic, reproductive, tumor, and treatment characteristics on TEXB levels. TEXB-alpha (due to persistent organohalogenated chemicals) and TEXB-beta (due mainly to endogenous estrogens) were quantified in 44 women. TEXB values significantly increased over follow-up (p
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In utero exposure to mixtures of Xenoestrogens and child neuropsychological development
Environmental Research, 2014Co-Authors: Nadia Vilahur, Mariana F. Fernández, Mariona Bustamante, Rosa Ramos, Joan Forns, Ferran Ballester, Mario Murcia, Isolina Riaño, Jesús Ibarluzea, Nicolás OleaAbstract:Abstract Background To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of Xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of Xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. Methods Cumulative prenatal exposure to Xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1–2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4–5 years of age. Interactions with sex were investigated. Results After adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1–2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found. Conclusions Our results suggest that boys’ early motor development might be more vulnerable to prenatal exposure to mixtures of Xenoestrogens, but associations do not persist in preschool children.
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Predictors of the total effective Xenoestrogen burden (TEXB) in human adipose tissue. A pilot study.
Reproductive Toxicology, 2011Co-Authors: Juan P. Arrebola, Mariana F. Fernández, J.m. Molina-molina, Piedad Martin-olmedo, José Expósito, Nicolás OleaAbstract:The estrogenicity of biological extracts tested by appropriate bioassay is a standard method to evaluate the total effective Xenoestrogen burden (TEXB). Information has been published on the combined effect of Xenoestrogens after removing endogenous hormones. The main goal of the present study was to investigate the combined estrogenicity of endogenous and Xenoestrogens in human adipose tissue samples with and without HPLC fractionation. The results suggest that both approaches may be useful to study interaction between Xenoestrogens and endogenous hormones. TEXB of the whole extract provides information about the overall estrogenicity to which humans are exposed, useful to assess the potential contribution to health outcomes. Additionally, it is possible to identify the source and potency of the estrogenicity by using the method with fractionation, distinguishing the effect of organohalogenated chemicals (alpha-fraction) from that of endogenous hormones and more polar Xenoestrogens (beta-fraction). Both methods are an integrative measure of internal estrogen load.
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assessment of the total effective Xenoestrogen burden in extracts of human placentas
Biomarkers, 2009Co-Authors: Mariajose Lopezespinosa, Elisabete Silva, Andreas Kortenkamp, Mariana F. Fernández, Josemanuel Molinamolina, Fatima Oleaserrano, Alicia Granada, Clemente Aguilargarduno, Nicolás OleaAbstract:We have standardized a method to assess the total effective Xenoestrogen burden (TEXB) in human placentas by the extraction and separation by high-performance liquid chromatography of two fractions containing lipophilic Xenoestrogens (alpha) and endogenous hormones (beta), followed by assessing their estrogenicity in MCF-7 breast cancer cell-based E-Screen and Yeast Estrogen Screen (YES) bioassays. The means of TEXB alpha concentrations (in estradiol equivalent (Eeq) units) were 1.32 and 0.77 Eeq pM g(-1) placenta in the E-Screen and YES, respectively; TEXB beta concentrations were 6.97 and 11.56 Eeq pM g(-1) placenta, respectively. The interclass correlation coefficient was low and a fair level of agreement was observed after kappa test correction. According to the E-Screen and YES, TEXB alpha was > or = LOD in 70.0 and 55.0% of the placentas and 92.5 and 82.5% in beta, respectively. Although both bioassays can be recommended for assessing TEXB, there is greater experience with the use of the E-Screen for estrogenic assessment after extensive extraction of complex human matrices.
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The total effective Xenoestrogen burden, a biomarker of exposure to Xenoestrogen mixtures, is predicted by the (anti)estrogenicity of its components.
Reproductive Toxicology, 2008Co-Authors: Mariana F. Fernández, Juan P. Arrebola, J.m. Molina-molina, Clemente Aguilar-garduño, Nicolás OleaAbstract:Appropriate biomarkers of human exposure are required for epidemiological studies of endocrine disruption. We addressed this issue by improving a standardized method to assess the total effective Xenoestrogen burden (TEXB), a biomarker of Xenoestrogen exposure. Extensive separation of Xenoestrogens from endogenous hormones was made in 20 adipose tissue samples by HPLC, and two eluates were separated and tested in the E-Screen bioassay. An extensive fractionation protocol was also developed. The objective of this study was to investigate predictors of TEXB by using a multiple regression model after adjusting by confounding factors. The final model included the estrogenicity of 8 out of 11 individual 1-min fractions into which the Xenoestrogen eluate was split and the marital status of patients, and it explained 97% of TEXB variability, and variables. Our results indicate that TEXB of complex mixtures can be accurately predicted from the estrogenicity of a small number of components.
Hani Elnezami - One of the best experts on this subject based on the ideXlab platform.
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combined low dose zearalenone and aflatoxin b1 on cell growth and cell cycle progression in breast cancer mcf 7 cells
Toxicology Letters, 2017Co-Authors: Alice S T Wong, Kenneth S. Korach, Hani ElnezamiAbstract:Abstract Zearalenone (ZEA) has long been recognized as a Xenoestrogen, while the endocrine disrupting effects of aflatoxin B1 (AFB1) have been identified recently. Due to co-occurrence and endocrine disrupting potentials of ZEA and AFB1, it was hypothesized that co-exposure to ZEA and AFB1 might affect breast cancer cell growth. Consequently, the aim of this study was to evaluate the combined effects of ZEA and AFB1 (1 nM–100 nM) on cell growth and cell cycle progression, using a human breast cancer cell line MCF-7. Our results showed that ZEA and AFB1 produced significant interactive effects on cell growth, DNA synthesis and cell cycle progression. While ZEA promoted growth, DNA synthesis and cell cycle progression, AFB1 was cytotoxic and counteracted the effects of ZEA. ZEA altered the expression of several breast cancer related genes, whereas AFB1 had minimal effects on gene expression. With the use of specific inhibitors, ERα, GPER and MAPK pathways were found to be responsible for ZEA’s effects on cell growth; while MAPK pathways might be involved in cytotoxic effects by AFB1. This study is first to report the effects of co-exposure of ZEA and AFB1 on breast cancer cell growth, possibly through ER dependent pathway. This suggested that endocrine-disrupting mycotoxins that co-occur in human food can interact and influence human health. Future work on interactive effects of endocrine-disrupting mycotoxins or other Xenoestrogens is warranted, which will contribute to improved risk assessments.
Mariana F. Fernández - One of the best experts on this subject based on the ideXlab platform.
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changes in the total effective Xenoestrogen burden texb of breast cancer patients during an 18 month post surgical follow up
Reproductive Toxicology, 2017Co-Authors: Juan P. Arrebola, Mariana F. Fernández, Nicolás Olea, Jose Pumarega, Miquel Porta, Josemanuel MolinamolinaAbstract:Abstract We aimed to assess changes in the total effective Xenoestrogen burden (TEXB) −a biomarker of combined effect of mixtures of Xenoestrogens- in breast cancer patients at surgery (breast adipose tissue) and at different time points during an 18-month follow-up (abdominal adipose tissue), and to analyze the potential influence of socio-demographic, reproductive, tumor, and treatment characteristics on TEXB levels. TEXB-alpha (due to persistent organohalogenated chemicals) and TEXB-beta (due mainly to endogenous estrogens) were quantified in 44 women. TEXB values significantly increased over follow-up (p
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In utero exposure to mixtures of Xenoestrogens and child neuropsychological development
Environmental Research, 2014Co-Authors: Nadia Vilahur, Mariana F. Fernández, Mariona Bustamante, Rosa Ramos, Joan Forns, Ferran Ballester, Mario Murcia, Isolina Riaño, Jesús Ibarluzea, Nicolás OleaAbstract:Abstract Background To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of Xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of Xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. Methods Cumulative prenatal exposure to Xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1–2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4–5 years of age. Interactions with sex were investigated. Results After adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1–2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found. Conclusions Our results suggest that boys’ early motor development might be more vulnerable to prenatal exposure to mixtures of Xenoestrogens, but associations do not persist in preschool children.
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Predictors of the total effective Xenoestrogen burden (TEXB) in human adipose tissue. A pilot study.
Reproductive Toxicology, 2011Co-Authors: Juan P. Arrebola, Mariana F. Fernández, J.m. Molina-molina, Piedad Martin-olmedo, José Expósito, Nicolás OleaAbstract:The estrogenicity of biological extracts tested by appropriate bioassay is a standard method to evaluate the total effective Xenoestrogen burden (TEXB). Information has been published on the combined effect of Xenoestrogens after removing endogenous hormones. The main goal of the present study was to investigate the combined estrogenicity of endogenous and Xenoestrogens in human adipose tissue samples with and without HPLC fractionation. The results suggest that both approaches may be useful to study interaction between Xenoestrogens and endogenous hormones. TEXB of the whole extract provides information about the overall estrogenicity to which humans are exposed, useful to assess the potential contribution to health outcomes. Additionally, it is possible to identify the source and potency of the estrogenicity by using the method with fractionation, distinguishing the effect of organohalogenated chemicals (alpha-fraction) from that of endogenous hormones and more polar Xenoestrogens (beta-fraction). Both methods are an integrative measure of internal estrogen load.
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assessment of the total effective Xenoestrogen burden in extracts of human placentas
Biomarkers, 2009Co-Authors: Mariajose Lopezespinosa, Elisabete Silva, Andreas Kortenkamp, Mariana F. Fernández, Josemanuel Molinamolina, Fatima Oleaserrano, Alicia Granada, Clemente Aguilargarduno, Nicolás OleaAbstract:We have standardized a method to assess the total effective Xenoestrogen burden (TEXB) in human placentas by the extraction and separation by high-performance liquid chromatography of two fractions containing lipophilic Xenoestrogens (alpha) and endogenous hormones (beta), followed by assessing their estrogenicity in MCF-7 breast cancer cell-based E-Screen and Yeast Estrogen Screen (YES) bioassays. The means of TEXB alpha concentrations (in estradiol equivalent (Eeq) units) were 1.32 and 0.77 Eeq pM g(-1) placenta in the E-Screen and YES, respectively; TEXB beta concentrations were 6.97 and 11.56 Eeq pM g(-1) placenta, respectively. The interclass correlation coefficient was low and a fair level of agreement was observed after kappa test correction. According to the E-Screen and YES, TEXB alpha was > or = LOD in 70.0 and 55.0% of the placentas and 92.5 and 82.5% in beta, respectively. Although both bioassays can be recommended for assessing TEXB, there is greater experience with the use of the E-Screen for estrogenic assessment after extensive extraction of complex human matrices.
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The total effective Xenoestrogen burden, a biomarker of exposure to Xenoestrogen mixtures, is predicted by the (anti)estrogenicity of its components.
Reproductive Toxicology, 2008Co-Authors: Mariana F. Fernández, Juan P. Arrebola, J.m. Molina-molina, Clemente Aguilar-garduño, Nicolás OleaAbstract:Appropriate biomarkers of human exposure are required for epidemiological studies of endocrine disruption. We addressed this issue by improving a standardized method to assess the total effective Xenoestrogen burden (TEXB), a biomarker of Xenoestrogen exposure. Extensive separation of Xenoestrogens from endogenous hormones was made in 20 adipose tissue samples by HPLC, and two eluates were separated and tested in the E-Screen bioassay. An extensive fractionation protocol was also developed. The objective of this study was to investigate predictors of TEXB by using a multiple regression model after adjusting by confounding factors. The final model included the estrogenicity of 8 out of 11 individual 1-min fractions into which the Xenoestrogen eluate was split and the marital status of patients, and it explained 97% of TEXB variability, and variables. Our results indicate that TEXB of complex mixtures can be accurately predicted from the estrogenicity of a small number of components.
Airo Tsubura - One of the best experts on this subject based on the ideXlab platform.
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Effects of prepubertal exposure to Xenoestrogen on development of estrogen target organs in female CD-1 mice
in Vivo, 2005Co-Authors: Yasuyoshi Nikaido, Naoyuki Danbara, Miki Tsujita-kyutoku, Takashi Yuri, Norihisa Uehara, Airo TsuburaAbstract:Background: There have been no previous reports comparing the effects of prepubertal Xenoestrogen exposure on development of the reproductive tract and mammary glands in female mice. The effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), zeranol (ZER), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Materials and Methods: Beginning at 15 days of age, female CD-1 mice were administered 4 daily subcutaneous injections of 10 mg/kg/day of GEN, RES, ZEA, ZER or BPA, or 10 Ig/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle. Vaginal opening was checked; estrous cyclicity was monitored from 5, 9 or 21 weeks of age for 21 consecutive days; 6 animals per group were autopsied at 4, 8 and 24 weeks of age. Results: Prepubertal exposure to GEN, ZEA, ZER and DES (but not RES or BPA) accelerated puberty onset (vaginal opening). Vaginal smears indicated that all Xenoestrogen- treated mice were cycling, but ZEA-, ZER- and DES-treated mice spent more time in estrus. At 4 weeks of age, absence of corpora lutea (anovulatory ovary) was observed in the untreated controls (33%, 2/6) and the GEN (50%, 3/6), RES (50%, 3/6), ZEA (100%, 6/6), ZER (100%, 6/6), BPA (83%, 5/6) and DES groups (100%, 6/6). At 8 weeks of age, absence of corpora lutea was observed in the ZEA (33%, 2/6) group. Corpora lutea were present in all mice sacrificed at 24 weeks of age. Groups that received prepubertal Xenoestrogen injections exhibited no morphological abnormalities of the uterus and vagina, and exhibited mammary gland growth similar to that of the untreated controls at all time-points. Conclusion: GEN, ZEA, ZER and DES (but not RES or BPA) caused early vaginal opening; mice exposed to ZEA, ZER or DES spent more time in the estrus phase; ZEA-treated mice had a longer period of anovulatory ovary than other Xenoestrogen-treated mice; however, none of the Xenoestrogens tested altered the uterine or vaginal morphology or mammary gland growth. Xenoestrogens (chemicals with estrogenic activity) are endocrine-disrupting chemicals that include naturally occurring substances produced by plants (phytoestrogens), molds (mycoestrogens) and man-made chemicals released into the environment (1). They may be ingested directly in plant material, in the tissues of animals that ingest Xenoestrogen-producing plants or plants infected by Xenoestrogen-producing molds, or in foodstuffs contaminated by release of Xenoestrogens from polycarbonate plastic plates. Exposure to Xenoestrogens during critical stages of growth can interfere with the development and differentiation of estrogen target organs (2). These effects can be severe, particularly in prepubertal children, whose endogenous estrogen concentration is low (3). There is evidence that exposure of humans to the Xenoestrogen diethylstilbestrol (DES; (E)-3,4-bis (4-hydroxyphenyl)-3-hexene) alters the development of estrogen target organs. In utero exposure to DES as an anti-abortive has been found to induce clear cell adenocarcinoma of the vagina in daughters after puberty (4). Although the DES-exposed daughters in that study had low risk of development of clear cell adenocarcinoma (
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effects of prepubertal exposure to Xenoestrogen on development of estrogen target organs in female cd 1 mice
in Vivo, 2005Co-Authors: Yasuyoshi Nikaido, Naoyuki Danbara, Takashi Yuri, Norihisa Uehara, Miki Tsujitakyutoku, Airo TsuburaAbstract:Background: There have been no previous reports comparing the effects of prepubertal Xenoestrogen exposure on development of the reproductive tract and mammary glands in female mice. The effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), zeranol (ZER), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Materials and Methods: Beginning at 15 days of age, female CD-1 mice were administered 4 daily subcutaneous injections of 10 mg/kg/day of GEN, RES, ZEA, ZER or BPA, or 10 Ig/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle. Vaginal opening was checked; estrous cyclicity was monitored from 5, 9 or 21 weeks of age for 21 consecutive days; 6 animals per group were autopsied at 4, 8 and 24 weeks of age. Results: Prepubertal exposure to GEN, ZEA, ZER and DES (but not RES or BPA) accelerated puberty onset (vaginal opening). Vaginal smears indicated that all Xenoestrogen- treated mice were cycling, but ZEA-, ZER- and DES-treated mice spent more time in estrus. At 4 weeks of age, absence of corpora lutea (anovulatory ovary) was observed in the untreated controls (33%, 2/6) and the GEN (50%, 3/6), RES (50%, 3/6), ZEA (100%, 6/6), ZER (100%, 6/6), BPA (83%, 5/6) and DES groups (100%, 6/6). At 8 weeks of age, absence of corpora lutea was observed in the ZEA (33%, 2/6) group. Corpora lutea were present in all mice sacrificed at 24 weeks of age. Groups that received prepubertal Xenoestrogen injections exhibited no morphological abnormalities of the uterus and vagina, and exhibited mammary gland growth similar to that of the untreated controls at all time-points. Conclusion: GEN, ZEA, ZER and DES (but not RES or BPA) caused early vaginal opening; mice exposed to ZEA, ZER or DES spent more time in the estrus phase; ZEA-treated mice had a longer period of anovulatory ovary than other Xenoestrogen-treated mice; however, none of the Xenoestrogens tested altered the uterine or vaginal morphology or mammary gland growth. Xenoestrogens (chemicals with estrogenic activity) are endocrine-disrupting chemicals that include naturally occurring substances produced by plants (phytoestrogens), molds (mycoestrogens) and man-made chemicals released into the environment (1). They may be ingested directly in plant material, in the tissues of animals that ingest Xenoestrogen-producing plants or plants infected by Xenoestrogen-producing molds, or in foodstuffs contaminated by release of Xenoestrogens from polycarbonate plastic plates. Exposure to Xenoestrogens during critical stages of growth can interfere with the development and differentiation of estrogen target organs (2). These effects can be severe, particularly in prepubertal children, whose endogenous estrogen concentration is low (3). There is evidence that exposure of humans to the Xenoestrogen diethylstilbestrol (DES; (E)-3,4-bis (4-hydroxyphenyl)-3-hexene) alters the development of estrogen target organs. In utero exposure to DES as an anti-abortive has been found to induce clear cell adenocarcinoma of the vagina in daughters after puberty (4). Although the DES-exposed daughters in that study had low risk of development of clear cell adenocarcinoma (<1%), DES was associated with increased frequency of benign reproductive tract dysfunction and structural abnormality. Many experiments using rodent models have shown strikingly similar abnormalities after exposure to DES in early life (5); mouse models have proven to be effective for the examination of abnormalities in estrogen target organs. Naturally occurring and man-made chemicals that exhibit estrogenic biological activity are widely distributed in the environment (1). Among the chemicals that exhibit such activity are genistein (GEN), resveratrol (RES), zearalenone (ZEA), zeranol (·-zearalanol; ZER) and bisphenol A (BPA). GEN (4', 5, 7-trihydroxy isoflavone) is a major component of soy-based foods. It is estimated that infants
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effects of maternal Xenoestrogen exposure on development of the reproductive tract and mammary gland in female cd 1 mouse offspring
Reproductive Toxicology, 2004Co-Authors: Yasuyoshi Nikaido, Naoyuki Danbara, Takashi Yuri, Norihisa Uehara, Miki Tsujitakyutoku, Katsuhiko Yoshizawa, Airo TsuburaAbstract:Abstract The objective of this study was to examine the effects of maternal exposure to Xenoestrogen, at levels comparable to or greater than human exposure, on development of the reproductive tract and mammary glands in female CD-1 mouse offspring. Effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Beginning on gestational day 15, pregnant CD-1 mice were administered four daily subcutaneous injections with 0.5 or 10 mg/kg/day of GEN, RES, ZEA or BPA, 0.5 or 10 μg/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle ( n = 6). Vaginal opening was monitored, 6 animals per group were autopsied at 4, 8, 12 and 16 weeks of age and estrous cyclicity was monitored from 9 to 11 weeks of age. Maternal exposure to Xenoestrogen accelerated puberty onset (vaginal opening) and increased the length of the estrous cycle; mice treated with GEN, RES, BPA or DES spent more time in diestrus, and ZEA-treated mice spent more time in estrus. Lack of corpora lutea and vaginal cornification were observed at 4 weeks of age in the high-dose GEN (33%) and RES (17%) groups, and in the high- and low-dose BPA groups (33 and 50%, respectively) and DES groups (83 and 100%, respectively). Lack of corpora lutea and vaginal cornification was observed in the high-dose ZEA group at 4, 8, 12 and 16 weeks of age (83, 100, 83 and 33%, respectively). Mammary gland differentiation was accelerated in ZEA- and BPA-treated mice with corpora lutea at 4 weeks of age. ZEA-treated mice without corpora lutea showed mammary growth arrest at 8, 12 and 16 weeks of age; their mammary glands consisted only of a dilatated duct filled with secreted fluid. Mammary gland growth was similar with Xenoestrogens other than ZEA or BPA to that of the controls at all time points. High-dose GEN and RES and high- and low-dose BPA and DES exerted transient effects on the reproductive tract and mammary glands, whereas ZEA exerted prolonged effects.
Alice S T Wong - One of the best experts on this subject based on the ideXlab platform.
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combined low dose zearalenone and aflatoxin b1 on cell growth and cell cycle progression in breast cancer mcf 7 cells
Toxicology Letters, 2017Co-Authors: Alice S T Wong, Kenneth S. Korach, Hani ElnezamiAbstract:Abstract Zearalenone (ZEA) has long been recognized as a Xenoestrogen, while the endocrine disrupting effects of aflatoxin B1 (AFB1) have been identified recently. Due to co-occurrence and endocrine disrupting potentials of ZEA and AFB1, it was hypothesized that co-exposure to ZEA and AFB1 might affect breast cancer cell growth. Consequently, the aim of this study was to evaluate the combined effects of ZEA and AFB1 (1 nM–100 nM) on cell growth and cell cycle progression, using a human breast cancer cell line MCF-7. Our results showed that ZEA and AFB1 produced significant interactive effects on cell growth, DNA synthesis and cell cycle progression. While ZEA promoted growth, DNA synthesis and cell cycle progression, AFB1 was cytotoxic and counteracted the effects of ZEA. ZEA altered the expression of several breast cancer related genes, whereas AFB1 had minimal effects on gene expression. With the use of specific inhibitors, ERα, GPER and MAPK pathways were found to be responsible for ZEA’s effects on cell growth; while MAPK pathways might be involved in cytotoxic effects by AFB1. This study is first to report the effects of co-exposure of ZEA and AFB1 on breast cancer cell growth, possibly through ER dependent pathway. This suggested that endocrine-disrupting mycotoxins that co-occur in human food can interact and influence human health. Future work on interactive effects of endocrine-disrupting mycotoxins or other Xenoestrogens is warranted, which will contribute to improved risk assessments.
