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RECORD NUMBER: 6 OF 15

OLS Field Name OLS Field Data
Main Title 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.
Author Mass, M. J. ; Jeffers, A. J. ; Ross, J. A. ; Nelson, G. ; Galati, A. J. ;
CORP Author 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.
Publisher c1993
Year Published 1993
Report Number EPA/600/J-94/066;
Stock Number PB94-139557
Additional Subjects Ras genes ; Mutation ; Neoplasms ; DNA adducts ; Benzo(a)pyrene ; Lung ; Toxicology ; Codon ; Mice ; DNA sequence analysis ; Deoxyribonucleic acids ; Reprints ; Benz(j)aceanthrylene
Holdings
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Status
NTIS  PB94-139557 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 05/14/1994
Collation 8p
Abstract
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.