Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung.

Published

Journal Article

This study was undertaken to evaluate the carcinogenic potential of 5-methylchrysene (5-MeC) in strain A/J mouse lung and to correlate the 5-MeC-DNA adduct profile in lung tissue with the mutation spectrum in the K-ras gene of lung tumors. Strain A/J mice received a single i.p. injection of 5-MeC at doses of 10, 50, 100 and 200 mg/kg and after 24, 48 and 72 h their lungs were collected for DNA adduct analysis. Eight months later, lungs from the remaining mice were harvested and the lung tumors counted and collected for subsequent mutational analysis of the K-ras gene. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. Six 5-MeC-DNA adducts were observed; one adduct comigrated with the standard N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I [1R,2S,3S-trihydroxy-4R-(N2-deoxy-guanosyl-3'-phosphate)- 1,2,3,4-tetrahydro-5-methyl-chrysene], derived from the bay-region diol-epoxide of 5-MeC. DNAs isolated from 5-MeC-induced lung tumors were evaluated for activating mutations in the K-ras gene by polymerase chain reaction-single strand conformation polymorphism and direct DNA sequencing analysis. Mutations were detected in 44 of 49 (90%) 5-MeC-induced tumors and the mutations were GGT-->TGT (50%), GGT-->GTT (23%) and GGT-->CGT (27%) in codon 12 of the gene. These results suggest that the N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I may be one of the promutagenic adducts of 5-MeC in strain A/J mouse lung.

Full Text

Duke Authors

Cited Authors

  • You, L; Wang, D; Galati, AJ; Ross, JA; Mass, MJ; Nelson, GB; Wilson, KH; Amin, S; Stoner, JC; Nesnow, S

Published Date

  • November 1994

Published In

Volume / Issue

  • 15 / 11

Start / End Page

  • 2613 - 2618

PubMed ID

  • 7955114

Pubmed Central ID

  • 7955114

International Standard Serial Number (ISSN)

  • 0143-3334

Digital Object Identifier (DOI)

  • 10.1093/carcin/15.11.2613

Language

  • eng

Conference Location

  • England