You are here:
K-RAS MUTATIONS AND ADDUCTS FORMED BY BENZ(J)ACEANTHRYLENE AND BENZO(A)PYRENE IN THE LUNGS OF STRAIN A/J MICE
Citation:
Mass, M., A. Jeffers, J. Ross, G. Nelson, T. Galati, G. Stoner, AND S. Nesnow. K-RAS MUTATIONS AND ADDUCTS FORMED BY BENZ(J)ACEANTHRYLENE AND BENZO(A)PYRENE IN THE LUNGS OF STRAIN A/J MICE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/066 (NTIS PB94139557), 1993.
Description:
Strain A/J mice received l.p. injections of benz[j]aceanthrylene (B[j]A) or benzo(a)pyrene (BP) and lung tissues were removed for analysis of BP- or B [j] A-derived DNA adducts during the first three days of exposure. roup of animals exposed to these hydrocarbons was held for eight months to determine lung tumor incidences, the occurrence at mutations in codons 12 or codon 61 of the K-ras oncogene in tumors that arose, and the relationship between K-ras oncogene mutations in tumors and the presence and quantity of genomic DNA adducts. he major DNA adduct in the lungs of mice exposed to BP was BPDE-l-dGuo arising from bay region diol epoxide activation of BP and was consistent with the occurrence of tumors with mutations GGT-TGT (45%), GGT-GTT (20%), and GGT-GAT (15%) in codon 12, all involving mutations of G. B[j]A, a demethylated analog of 3-methylcholanthrene (3-MCA) with an unsaturated cyclopenta-ring produced 16 to 60-fold more tumors by dose than BP and the mutations in tumors were: GGT-CGT (66%), GGT-GTT (30%), GGT-TGT (4%); analysis of adduction patterns in DNA suggest that B[j]A is activated In strain A/J mouse lungs mostly at the cyclopenta-ring to DNA binding derivatives even though it contains a bay-region. he mutation spectrum induced by 3-MCA in K-ras codon 12 of mouse cells found in the published literature is similar to BP, but not to its close relative B[j]A. n contrast to B[j]A, 3-MCA is activated mostly via a bay region diol epoxide since its cyclopenta ring is saturated and not easily epoxidated. herefore, we propose that the GGT-CGT mutations produced by B[j]A In K-ras codon 12 are mostly the result of cyclopenta-ring derived adducts.