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CYCLOPENTA[CD]PYRENE-INDUCED TUMORIGENICITY, KI-RAS CODON 12 MUTATIONS AND DNA ADDUCTS IN STRAIN A/J MOUSE LUNG
Citation:
Nesnow, S., J. Ross, G. Nelson, K. Wilson, B. Roop, A. Jeffers, A. Galati, G. Stoner, AND R. Sangaiah. CYCLOPENTA[CD]PYRENE-INDUCED TUMORIGENICITY, KI-RAS CODON 12 MUTATIONS AND DNA ADDUCTS IN STRAIN A/J MOUSE LUNG. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/050.
Description:
Cyclopenta[cd]pyrene (CPP) is a ubiquitous cyclopenta-fused polycyclic aromatic hydrocarbon. PP is highly genotoxic in bacterial and mammalian systems inducing gene mutations, sister-chromatid exchanges, and morphological transformation. PP is a mouse skin carcinogen, a mouse skin tumor initiator and induces pulmonary tumors in newborn mice. e have examined the tumorigenic activity of CPP in strain A/J mice, have determined the formation and persistence of CPP-induced DNA adducts in lung tissue, and analyzed the mutational spectrum in the Ki-ras oncogene from CPP-induced tumors. e conclude that CPP is highly tumorigenic in the strain A/J mouse lung adenoma model, being 5 x that of B(a]P. his is unlike the result of CPP as a mouse skin tumorigen or tumor initiator in which CPP is considerably less potent than B[a]P. he increased activity of CPP may be related to the unique induction of the GGT-CGT, Ki-ras codon 12 mutation. his conclusion is supported by related results observed with another cyclopenta-PAH, benz[j]aceanthrylene.