title: Neonatal exposure of 17β-estradiol has no effects on mutagenicity of 7,12-dimethylbenz [a] anthracene in reproductive tissues of adult mice.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 USA ; Tianjin Medical University General Hospital, Tianjin, 300052 China.
authors.forename: Zhuhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 USA ; Xinjiang Institute for Food and Drug Control, Urumqi, Xinjiang 830004 China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 USA.
authors.forename: Mugimane G
authors.initials: MG
authors.lastname: Manjanatha
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Mei
keywords: 17 β-estradiol; Mammary gland; Mutagenicity; Neonatal exposure; Ovary