Relationship between Tumorigenic Potency, Ki-ras Codon 12 Mutations, and DNAAdducts Induced by Cyclopenta(cd)pyrene

摘要

Cyclopenta(cd)pyrene (CPP) was examined for its lung tumorigenic activity instrain 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 turmors. CPP displayed high tumorigenic activity, including 97.7 lung adenomas/mouse at 200 mg/kg. Ki-ras codon 12 mutations in the DNA of induced tumors were: GGT --> CGT (50%); GGT --> GTT (15%); GGT --> TGT (25%); GGT --> GAT (10%). All 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. (Copyright (c) 1994 Gordon and Breach Science Publishers S.A.)