Identification of cocarcinogens and their potential mechanisms of action using C3H10T 1/2 CL8 mouse embryo fibroblasts.
The cocarcinogenic action of five agents which increase microsomal mixed-function oxidase activity in vivo was examined in the C3H10T 1/2 CL8 transformation assay. The compounds studied were benz(a)anthracene, 5,6-benzoflavone, phenobarbital, pregnenolone-16 alpha-carbonitrile, and Aroclor 1254. After a 48-hr pretreatment with the agent, the cells were then treated with benzo(a)pyrene [B(a)P] and the agent for an additional 24 hr. All agents except for Aroclor 1254 increased B(a)P-mediated transformation in C3H10T 1/2 CL8 cells. Benz(a)anthracene, 5,6-benzoflavone, phenobarbital, and pregnenolone-16 alpha-carbonitrile also increased the overall metabolism of B(a)P in C3H10T 1/2 CL8 cells to 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene; 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9-hydroxybenzo(a)pyrene, and 3-hydroxybenzo(a)pyrene. Growth studies indicated that all four agents had no stimulatory effect which might have explained the increases in transformation frequency. This suggests that these agents exert their cocarcinogenic action via increases in the enzyme-mediated pathways of B(a)P metabolism.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003043:Cocarcinogenesis; D004790:Enzyme Induction / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology
D001140:Aroclors; D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D001580:Benzopyrenes; D011285:Pregnenolone Carbonitrile; D001564:Benzo(a)pyrene; D006899:Mixed Function Oxygenases; D010634:Phenobarbital