Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin treated intact but not ovariectomized rats

Angelika M. Tritscher, Andrew M. Seacat, James D Yager, John Davis Groopman, Brian D. Miller, Douglas Bell, Thomas R. Sutter, George W. Lucier

Research output: Contribution to journalArticle

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a more potent hepatocarcinogen in female than in male or ovariectomized rats. A possible mechanism for this increased sensitivity is through enhanced metabolic activation of estrogens by TCDD-induced enzymes leading to oxidative damage in the cell. As a marker for oxidative DNA damage, 8-oxo-deoxyguanosine (8-oxo-dG) was quantitated in livers of intact and ovariectomized Sprague-Dawley rats chronically treated with TCDD (125 ng/kg per day) with and without diethylnitrosamine as initiator. Elevated levels of 8-oxo-dG were detected in a significantly greater number of the intact compared to ovariectomized TCDD-treated rats. Expression of CYP1B1 mRNA, a newly identified cytochrome P450 with proposed estrogen hydroxylase activity, was highly induced by TCDD. The results are consistent with the hypothesis that increased metabolism of endogenous estrogens to catechols by TCDD-induced enzymes may lead to increased oxidative DNA damage and hence contribute to TCDD-mediated hepatocarcinogenicity in female rats.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalCancer Letters
Volume98
Issue number2
DOIs
StatePublished - Jan 2 1996

Fingerprint

DNA Damage
Liver
Deoxyguanosine
Estrogens
Catechol Estrogens
Diethylnitrosamine
Enzymes
Mixed Function Oxygenases
Polychlorinated Dibenzodioxins
Cytochrome P-450 Enzyme System
Sprague Dawley Rats
Messenger RNA

Keywords

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • 8-oxo-deoxyguanosine
  • CYP1B1
  • Estrogens
  • Oxidative damage
  • RT-PCR

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin treated intact but not ovariectomized rats. / Tritscher, Angelika M.; Seacat, Andrew M.; Yager, James D; Groopman, John Davis; Miller, Brian D.; Bell, Douglas; Sutter, Thomas R.; Lucier, George W.

In: Cancer Letters, Vol. 98, No. 2, 02.01.1996, p. 219-225.

Research output: Contribution to journalArticle

Tritscher, Angelika M. ; Seacat, Andrew M. ; Yager, James D ; Groopman, John Davis ; Miller, Brian D. ; Bell, Douglas ; Sutter, Thomas R. ; Lucier, George W. / Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin treated intact but not ovariectomized rats. In: Cancer Letters. 1996 ; Vol. 98, No. 2. pp. 219-225.
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