The co-carcinogen benzo[e]pyrene increases the binding of a low dose of the carcinogen benzo[a]pyrene to DNA in Sencar mouse epidermis.
The mechanism of the co-carcinogenic activity of benzo[e]pyrene (BeP) was investigated by determining the effects of BeP on the binding of the carcinogen benzo[a]pyrene (BaP) to DNA in Sencar mouse epidermis. The dose of BaP used was 20 nmol/mouse, a dose which is not carcinogenic in a single application but is carcinogenic after multiple treatments such as those in the BaP-BeP co-carcinogenesis experiments described by Van Duuren and Goldschmidt (J. Natl. Cancer Inst., 56, 1237, 1976). After 3 h of exposure to [3H]BaP and BeP at BaP:BeP dose ratios of 1:3 and 1:10, [3H]BaP-DNA adducts in both BeP-treated groups were lower than in an acetone-BaP control group. After 12 and 24 h of exposure, the BaP-BeP (1:10) group contained 19% and 33% higher [3H]BaP-DNA adduct levels than the control. In the BaP-BeP (1:3) group, the amount of [3H]BaP-DNA adduct levels was higher than the control after 12 h. BeP co-treatment with either [3H]BaP-7,8-dihydrodiol or anti-[3H]BaPDE had no effect on the amount of BaPDE-DNA adducts present. These results demonstrate that the co-carcinogen BeP increases the amount of a low dose of BaP that binds to mouse epidermal DNA and indicate that the increase in BaP-DNA adducts results from increased metabolism of BaP to the proximate carcinogen BaP-7,8-dihydrodiol.
Lau
H H
HH
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Baird
W M
WM
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism*; D001580:Benzopyrenes / Q000008:administration & dosage / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003043:Cocarcinogenesis; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004249:DNA Damage; D004357:Drug Synergism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D051379:Mice
D001580:Benzopyrenes; D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; C026487:benzo(e)pyrene; D004247:DNA