||Ki-ras Oncogene Mutations in Tumors and DNA Adducts Formed by Benz(i)aceanthrylene and Benzo(a)pyrene in the Lungs of Strain A/J Mice.
Mass, M. J. ;
Jeffers, A. J. ;
Ross, J. A. ;
Nelson, G. ;
Galati, A. J. ;
||Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;Medical Coll. of Ohio at Toledo. Dept. of Pathology. ;Ohio State Univ., Columbus. Arthur James Cancer Hospital.;Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div.
Ras genes ;
DNA adducts ;
DNA sequence analysis ;
Deoxyribonucleic acids ;
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||Strain A/J mice received intraperitoneal injections of benz(j)aceanthrylene(B(j)A) or benzo(a)pyrene (B(a)P). At 24, 48, and 72 h, lung tissues were removed for analysis of B(a)P- or B(j)A-derived DNA adduct formation during the first 3 d of exposure. One group of mice exposed to these hydrocarbons was kept for 8 mo to determine lung tumor multiplicity, the occurrence of mutations in codons 12 and 61 of the Ki-ras gene in the tumors that arose, the relationship between Ki-ras oncogene mutations in tumors, and the presence and quantity of genomic DNA adducts. Analysis of adduction patterns in DNA suggested that B(j)A was activated to form DNA-binding derivatives in A/J mouse lungs primarily at the cyclopenta ring even though B(j)A contains a bay region. As reported in the published literature, the mutation spectrum induced by 3-MCA in Ki-ras codon 12 of mouse cells is similar to that of B(a)P but not to that of its close relative B(j)A. In 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. Therefore, we propose that the GGT --> CGT mutations produced by B(j)A in Ki-ras codon 12 were mostly the result of cyclopenta-ring-derived adducts.
||Pub. in Molecular Carcinogenesis 8, n3 p186-192 Nov 93. Prepared in cooperation with Medical Coll. of Ohio at Toledo. Dept. of Pathology, and Ohio State Univ., Columbus. Arthur James Cancer Hospital. Sponsored by Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div.
|NTIS Title Notes
||Reprint: Ki-ras Oncogene Mutations in Tumors and DNA Adducts Formed by Benz(i)aceanthrylene and Benzo(a)pyrene in the Lungs of Strain A/J Mice.
||PC A02/MF A01