PMID: 2502547Aug 5, 1989Paper

Replication blocks and sequence interaction specificities in the codon 12 region of the c-Ha-ras proto-oncogene induced by four carcinogens in vitro.

The Journal of Biological Chemistry
K MariënG Bailey

Abstract

We have examined the region surrounding codon 12 in the human c-Ha-ras proto-oncogene in vitro to determine the reaction intensities at the guanine nucleotides after exposure to the mycotoxin aflatoxin B1, to one of its human metabolites aflatoxin M1, to dimethyl sulfate, and to the major ultimate carcinogen of benzo(a)pyrene, benzo(a)pyrene diol-epoxide. Among the adducts produced, those at N-7-guanyl sites are alkali-labile and can be identified using a variation of the Maxam-Gilbert sequencing procedure. Data indicate that the guanine nucleotides of codon 12 have above average potential for adduct formation by the genotoxins when compared to other guanine sites, but were not the strongest sites. This codon 12 region has been inserted into single-stranded M13 phage, exposed to several of the genotoxins, and used as a template for DNA synthesis in vitro. There is a sequence-specific variation in polymerase inhibition at various adducted nucleotide sites, but replication blocks are not preferentially seen at the carcinogen-adducted guanines of codon 12. These results indicate that the predominance of point mutations which are detected in vivo at codon 12 do not reflect sequence-mediated preferential susceptibility of these site...Continue Reading

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.