Benzo(e)pyrene-induced Alterations in the Metabolic Activation of Benzo(a)pyrene and 7,12-Dimethylbenz(a)anthracene by Hamster Embryo Cells1

Benzo(e)pyrene (BeP) is a cocarcinogen with benzo(a)pyrene (BaP) and an anticarcinogen with 7,12-dimethylbenz(a)anthracene (DMBA) in mouse skin initiation-promotion assays (Slaga, T. J., Jecker, L., Bracken, W. M. and Weeks C. E. Cancer Lett. 7: 51-59, 1979). We have investigated the effects of BeP on the metabolic activation of BaP and DMBA in early-passage cultures of Syrian hamster embryo cells. BeP had no effect on BaP-induced mutation frequencies in hamster embryo cell-me diated assays with V79 target cells. However, it inhibited the DMBA-induced mutagenesis by as much as 10-fold at the highest dose tested. Low doses of BeP did not affect the total amount of BaP metabolized, but the proportion of water-soluble metabolites was reduced, and the proportions of frans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and frans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene were increased. Higher doses did decrease BaP me tabolism and caused similar alterations in the metabolite pro file. In cultures treated with frans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, BeP greatly reduced the oxidative metabolism of this diol. BeP inhibited DMBA metabolism at all doses tested; the proportion of water-soluble metabolites formed was de creased, and the proportions of frans-8,9-dihydro-8,9-dihydroxy7,12-dimethylbenz(a)anthracene and frans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz(a)anthracene were increased. The results demonstrate that BeP is an effective inhibitor of the secondary oxidation of carcinogenic hydrocarbon diols re quired to convert diols which are proximate carcinogens to ultimate carcinogens such as diol-epoxides. The balance be tween (a) limited inhibition with consequent increase in total exposure to the ultimate carcinogenic form and (b) sufficient inhibition to reduce exposure to the ultimate carcinogenic form may determine whether BeP acts as a coor anticarcinogen with a particular carcinogenic hydrocarbon.