Neonatal exposure of 17β-estradiol has no effects on mutagenicity of 7,12-dimethylbenz [a] anthracene in reproductive tissues of adult mice

Zhang, Zhuhong; Li, Haifang; Manjanatha, Mugimane G.; Chen, Tao; Mei, Nan

doi:10.1186/s41021-015-0011-y

Neonatal exposure of 17β-estradiol has no effects on mutagenicity of 7,12-dimethylbenz [a] anthracene in reproductive tissues of adult mice

Journal Article · Thu Jul 30 00:00:00 EDT 2015 · Genes and environment (Online)

DOI:https://doi.org/10.1186/s41021-015-0011-y· OSTI ID:1629916

Zhang, Zhuhong ^[1]; Li, Haifang ^[2]; Manjanatha, Mugimane G. ^[3]; Chen, Tao ^[3]; Mei, Nan ^[3]

National Center for Toxicological Research, Jefferson, AR (United States). Division of Genetic and Molecular Toxicology; Tianjin Medical Univ. General Hospital (China); DOE/OSTI
National Center for Toxicological Research, Jefferson, AR (United States). Division of Genetic and Molecular Toxicology; Xinjiang Institute for Food and Drug Control, Xinjiang (China)
National Center for Toxicological Research, Jefferson, AR (United States). Division of Genetic and Molecular Toxicology

Introduction: Biological studies in animals and epidemiological findings in humans clearly demonstrate that estrogens including 17β-estradiol (E2) are weak carcinogens via both genetic and epigenetic mechanisms. Carcinogenesis analyses have indicated that female mice exposed to E2 as neonates develop more mammary and ovarian tumors when compared to adult exposures. In the present study, Big Blue transgenic mice were used to investigate the effects of E2 on mutagenicity of 7,12-dimethylbenz [a] anthracene (DMBA), a genotoxic carcinogen, in mammary gland and ovary following neonatal exposure. Results: DMBA treatment resulted in significant increases in cII mutant frequencies (MFs) in both mammary glands and ovaries, with A:T → T:A transversion as the predominant type of mutation. However, co-exposure to E2 daily for the first 5 days after birth and to DMBA at 6 months of age did not significantly increase cII MFs compared to DMBA treatment alone. Further, there were also no significant differences in mutational spectra between DMBA exposure alone and E2 + DMBA treatment. Conclusion: These results suggest that early life exposures of mice to estrogens like E2 do not enhance mutagenicity by subsequent exposure to a chemical like DMBA in later life.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: SC0014664

OSTI ID:: 1629916

Journal Information:: Genes and environment (Online), Journal Name: Genes and environment (Online) Journal Issue: 1 Vol. 37; ISSN 1880-7062

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Neonatal exposure
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Neonatal exposure of 17β-estradiol has no effects on mutagenicity of 7,12-dimethylbenz [a] anthracene in reproductive tissues of adult mice

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