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Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

BACKGROUND: Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while g...

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Autores principales: Wang, Jun, Jenkins, Sarah, Lamartiniere, Coral A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049406/
https://www.ncbi.nlm.nih.gov/pubmed/24884420
http://dx.doi.org/10.1186/1471-2407-14-379
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author Wang, Jun
Jenkins, Sarah
Lamartiniere, Coral A
author_facet Wang, Jun
Jenkins, Sarah
Lamartiniere, Coral A
author_sort Wang, Jun
collection PubMed
description BACKGROUND: Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. METHODS: Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. RESULTS: Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. CONCLUSION: Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to genistein exposure alone. BPA + Gen increased cell proliferation at PND21, suggesting mammary gland maturation, and decreased cell proliferation while increasing apoptosis in PND50 rats, suggesting mammary chemoprevention. Differential expression of proteins involved in regulating cell proliferation and apoptosis lend support to these chemicals, both alone and in combination, altering mammary gland cancer susceptibility.
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spelling pubmed-40494062014-06-10 Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein Wang, Jun Jenkins, Sarah Lamartiniere, Coral A BMC Cancer Research Article BACKGROUND: Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. METHODS: Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. RESULTS: Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. CONCLUSION: Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to genistein exposure alone. BPA + Gen increased cell proliferation at PND21, suggesting mammary gland maturation, and decreased cell proliferation while increasing apoptosis in PND50 rats, suggesting mammary chemoprevention. Differential expression of proteins involved in regulating cell proliferation and apoptosis lend support to these chemicals, both alone and in combination, altering mammary gland cancer susceptibility. BioMed Central 2014-05-29 /pmc/articles/PMC4049406/ /pubmed/24884420 http://dx.doi.org/10.1186/1471-2407-14-379 Text en Copyright © 2014 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Wang, Jun
Jenkins, Sarah
Lamartiniere, Coral A
Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title_full Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title_fullStr Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title_full_unstemmed Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title_short Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein
title_sort cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol a and genistein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049406/
https://www.ncbi.nlm.nih.gov/pubmed/24884420
http://dx.doi.org/10.1186/1471-2407-14-379
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