Oxidative DNA damage in XPC-knockout and its wild mice treated with equine estrogen

Yoshinori Okamoto, Pei Hsin Chou, Yeon Kim Sung, Naomi Suzuki, Y. R.Santosh Laxmi, Kanako Okamoto, Xiaoping Liu, Tomonari Matsuda, Shinya Shibutani

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Long-term hormone replacement therapy with equine estrogens is associated with a higher risk of breast, ovarian, and endometrial cancers. Reactive oxygen species generated through redox cycling of equine estrogen metabolites may damage cellular DNA. Such oxidative stress may be linked to the development of cancers in reproductive organs. Xeroderma pigmentosa complementation group C-knockout (Xpc-KO) and wild-type mice were treated with equilenin (EN), and the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was determined as a marker of typical oxidative DNA damage, using liquid chromatography electrospray tandem mass spectrometry. The level of hepatic 8-oxodG in wild-type mice treated with EN (5 or 50 mg/kg/day) was significantly increased by approximately 220% after 1 week, as compared with mice treated with vehicle. In the uterus also, the level of 8-oxodG was significantly increased by more than 150% after 2 weeks. Similar results were observed with Xpc-KO mice, indicating that Xpc does not significantly contribute to the repair of oxidative damage. Oxidative DNA damage generated by equine estrogens may be involved in equine estrogen carcinogenesis.

Original languageEnglish
Pages (from-to)1120-1124
Number of pages5
JournalChemical Research in Toxicology
Volume21
Issue number5
DOIs
Publication statusPublished - 2008 May

All Science Journal Classification (ASJC) codes

  • Toxicology

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