Morphological transformation of C3H10T1/2CL8 cells by cyclopenta-fused derivatives of benzo[a]pyrene and benzo[e]pyrene.
Cyclopenta-fused homologs of polycyclic aromatic hydrocarbons (PAH) have proven to be more genotoxic and tumorigenic than their parent PAHs. In an effort to uncover their mechanisms of metabolic activation, the morphological transforming activities of dibenzo[k,mno]acephenanthrylene (CP(3,4)B[a]P), dibenzo[j,mno]acephenanthrylene (CP(1,12)B[a]P) and naphtho[1,2,3,4-mno]acephenanthrylene (CPB[e]P) were studied in C3H10T1/2CL8 mouse embryo fibroblasts. CP(3,4)B[a]P, a PAH with a blocked K region and unblocked bay region, was highly active inducing an average of 1.1 Type II and III foci/dish at 5 micrograms/ml with an average of 67% of the dishes containing foci. This activity was similar to that of benzo[a]pyrene. CP(1,12)B[a]P and CPB[e]P were inactive. The relative positions of the cyclopenta-ring and bay region may play an essential role in the metabolic activation of these PAHs and their biological activities.
Nesnow
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Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Beck
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S
Ball
L M
LM
Sangaiah
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Gold
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A
D000393:Air Pollutants / Q000378:metabolism / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects*; D008748:Methylcholanthrene / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011083:Polycyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000393:Air Pollutants; D001580:Benzopyrenes; D009153:Mutagens; D011083:Polycyclic Compounds; C070317:naphtho(1,2,3-mno)acephenanthrylene; C085416:dibenzo(k,mno)acephenanthrylene; C085417:dibenzo(j,mno)acephenanthrylene; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C026487:benzo(e)pyrene; C037411:benz(j)aceanthrylene