The
biological activities of
benzo(a)pyrene,
cyclopenta(c,d)pyrene, and 12 other structurally related compounds were assessed by mutagenicity studies with bacterial and mammalian cells and/or skin tumorigenicity studies with mice. The ability of the parent
hydrocarbons to be metabolically activated to mutagenic products was examined in strains TA98 and TA100 of Salmonella typhimurium, using 3 experimental protocols. In each case,
cyclopenta(c,d)pyrene was metabolically activated to products mutagenic to the bacteria to a greater extent than was
benzo(a)pyrene. However,
7,8-dihydrobenzo(a)pyrene and 0,10-dihydrobenzo(e)pyrene were the best substrates for metabolic activation to bacterial
mutagens. Highly purified
epoxide hydrase added to a purified and reconstituted
monooxygenase system readily abolished the mutagenic activity observed in strain TA100 of S. typhimurium when
cyclopenta(c,d)pyrene was the substrate, but not when
benzo(a)pyrene was the substrate. Inherent mutagenicity of several
epoxides of the
hydrocarbons generally paralleled the ability of their potential metabolic precursors to be activated to
mutagens.
1-Pyrenyloxirane and 10,11-dihydrocycloheptapyrene 8,9-oxide were highly mutagenic in strains TA98 and TA100 of S. typhimurium, and in the former strain these activities were comparable to that observed with
9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, 4-Pyrenyloxirane was significantly less mutagenic than was
1-pyrenyloxirane in both strains of bacteria and in mammalian cells.
Benzo(a)pyrene was over 20 times more tumorigenic than was
cyclopenta-(c,d)pyrene, and it was the most potent of the 11 compounds tested for
tumor-initiating activity in 2-stage initiation-promotion experiments on the skin of mice.
Cyclopenta(c,d)pyrene had
tumor-initiating activity comparable to that of
benzo-(a)anthracene, but it was significantly less active than
chrysene. Thus, contrary to inferences made from its high mutagenic activity,
cyclopenta(c,d)pyrene is a weak
tumor initiator on mouse skin.