Skip to main content
Article thumbnail
Location of Repository

Breast cancer 1 (BRCA1)-deficient embryos develop normally but are more susceptible to ethanol-initiated DNA damage and embryopathies

By Aaron M. Shapiro, Lutfiya Miller-Pinsler and Peter G. Wells

Abstract

The breast cancer 1 (brca1) gene is associated with breast and ovarian cancers, and heterozygous (+/−) brca1 knockout progeny develop normally, suggesting a negligible developmental impact. However, our results show BRCA1 plays a broader biological role in protecting the embryo from oxidative stress. Sox2-promoted Cre-expressing hemizygous males were mated with floxed brca1 females, and gestational day 8 +/− brca1 conditional knockout embryos with a 28% reduction in protein expression were exposed in culture to the reactive oxygen species (ROS)-initiating drug ethanol (EtOH). Untreated +/− brca1-deficient embryos developed normally, but when exposed to EtOH exhibited increased levels of oxidatively damaged DNA, measured as 8-oxo-2'-deoxyguanosine, γH2AX, which is a marker of DNA double strand breaks that can result from 8-oxo-2'-deoxyguanosine, formation, and embryopathies at EtOH concentrations that did not affect their brca1-normal littermates. These results reveal that even modest BRCA1 deficiencies render the embryo more susceptible to drug-enhanced ROS formation, and corroborate a role for DNA oxidation in the mechanism of EtOH teratogenesis

Topics: Breast cancer 1 (BRCA1), Oxidatively damaged DNA, DNA repair, Ethanol, Embryo culture, Embryopathies, Medicine (General), R5-920, Biology (General), QH301-705.5
Publisher: Elsevier
Year: 2016
DOI identifier: 10.1016/j.redox.2015.11.005
OAI identifier: oai:doaj.org/article:e2371794ce1c4f46939854edb66cbde3
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://doaj.org/toc/2213-2317 (external link)
  • http://www.sciencedirect.com/s... (external link)
  • https://doaj.org/article/e2371... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.