Role of cytochrome P450 enzyme induction in the metabolic activation of benzo[c]phenanthrene in human cell lines and mouse epidermis

Chemical Research in Toxicology
H J EinolfWilliam M Baird

Abstract

The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cells and the low activation of B[c]Ph in mouse skin, cells of the MCF-7 and the human hepatoma HepG2 cell lines were treated with the potent Ah receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to exposure to B[c]Ph for 24 h. Mice were treated topically with 1 microg of TCDD or vehicle (control) for 73 h and then with 2 micromol of B[c]Ph for 24 h. In MCF-7 cells, TCDD exposure increased B[c]PhDE-DNA adduct levels more than 3-fold with a 10-fold increase in the (-)-B[c]PhDE-2-dA(t) adduct. Treatment of HepG2 cells with TCDD prior to B[c]Ph application did not increase B[c]PhDE-DNA binding. Total B[c]PhDE-DNA adducts increased 3-fold in TCDD-treated mouse epidermis: the majority of the increase resulted from (+)-B[c]PhDE-1-dA adducts. Analysis of P450 enzymes by Western blotting detected a large increase of P4501B1 but almost no increase in P4501A1 in MCF-7 cells exposed to 10 microM B[c]Ph for 24 or 48...Continue Reading

References

Jan 1, 1992·Pharmacology & Therapeutics·J DiGiovanni
Oct 1, 1974·The Journal of Investigative Dermatology·T J SlagaS Thompson

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Citations

Apr 26, 2012·Chemical Research in Toxicology·Slobodan Rendic, F Peter Guengerich
Jun 13, 2002·Environmental Health Perspectives·Carl-Elis BoströmRoger Westerholm
Sep 21, 2001·Environmental Health Perspectives·L S Goldstein
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Dec 7, 2007·Drug Metabolism Reviews·Franz OeschRobert Landsiedel
Sep 11, 2002·Biochemical and Biophysical Research Communications·Zheying ZhuRobert J Edwards
May 1, 2013·Chemico-biological Interactions·Paweł BrzuzanMaciej Woźny
Mar 29, 2002·Environmental and Molecular Mutagenesis·Stephen S Hecht
Jul 17, 2008·The Journal of Clinical Endocrinology and Metabolism·Marianne CanonicoUNKNOWN Estrogen and Thromboembolism Risk (ESTHER) Study Group

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