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RELATIONSHIP BETWEEN TUMORIGENIC POTENCY, KI-#RAS# CODON 12 MUTATIONS AND DNA ADDUCTS INDUCED BY CYCLOPENTA[CD]PYRENE
Citation:
Nesnow, S., J. Ross, G. Nelson, K. Wilson, B.C. Roop, A. Jeffers, A. Galati, G. Stoner, R. Sangaiah, A. Gold, AND M. Mass. RELATIONSHIP BETWEEN TUMORIGENIC POTENCY, KI-#RAS# CODON 12 MUTATIONS AND DNA ADDUCTS INDUCED BY CYCLOPENTA[CD]PYRENE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/551.
Description:
Cyclopenta[cd]pyrene (CPP) was examined for its lung tumorigenic activity in strain A/J mice, for the formation and persistence of CPP-induced DNA adducts in lung tissue, and for its induction of mutations in the Ki-ras oncogene from CPP-induced tumors. PP displayed high tumorigenic activity inducing 97.7 lung adenomas/mouse at 200 mg/kg. i-ras codon 12 mutations in the DNA of induced tumors were: GGT-CGT (50%); GGT-GTT (15%); GGT-TGT (25%); GGT-GAT (10%). ll DNA adducts in the lungs of CPP-treated mice were CPP-3,4-oxide derived and most were CPP-3.4-oxide-2'-deoxyguanosine adducts. CPP is highly tumorigenic in the strain A/J mouse lung adenoma model, being 5 times more active than benzo[a]pyrene. The increased activity of CPP may be related to the unique induction of the GGT-CGT, Ki-ras codon 12 mutation.