Transformation of hamster embryo cells by epoxides and other derivatives of polycyclic hydrocarbons.

Abstract

K-region epoxides of dibenz(a,h)anthracene and benz(a)anthracene were more active in producing malignant transformation of hamster embryo cells than the corresponding hydrocarbons, K-regions cis - and trans -dihydrodiols and phenols. The cytotoxicity exerted by epoxides, relative to the other derivatives, varied among those tested. The 8,9-epoxide (non-K-region) of benz(a)anthracene was less active in producing transformation and cytotoxicity than the corresponding 5,6-epoxide (K-region). Expoxides of the K-regions of 3-methylcholanthrene, phenanthrene, and chrysene were also more active in producing cytotoxicity and transformation than the corresponding hydrocarbon. These data support the suggestion that the metabolic production of epoxides of these polycyclic hydrocarbons is a prerequisite for biological activity and that transformation by epoxides is not based on the selection of preexisting transformed cells. The K-region epoxide of 7-methylbenz(a)anthracene was slightly more active than 7-methylbenz(a)anthracene in producing transformation in a 4-hr treatment, but the converse was true with a 7-day exposure. Under both conditions, the activities of 7-bromomethyl-12-methylbenz(a)anthracene and 7-bromomethylbenz(a)anthracene were approximately the same as those of their parent hydrocarbons at producing transformation.