Assessment of mutations in Ki-ras and p53 in colon cancers from azoxymethane- and dimethylhydrazine-treated rats.

Abstract:

:Mutations in the Ki-ras oncogene and the p53 tumor suppressor gene are known to occur at high frequencies in human colon cancers. We measured the frequency of mutations in these two genes in colon adenocarcinomas obtained from a widely used experimental model of human colon carcinogenesis: F344 rats treated with the carcinogens azoxymethane (AOM) or dimethylhydrazine (DMH). We detected codon 12 mutations in Ki-ras in approximately 60% of colon adenocarcinomas induced by either carcinogen. We characterized the rat p53 intron-exon junctions to construct primers for polymerase chain reaction amplification of this gene. We discovered that the rat p53 gene was structurally different from the human p53 gene, as the rat gene was missing one intron between exons 6 and 7. Both single-stranded DNA conformational polymorphism analysis and direct DNA sequencing of the highly conserved regions of rat exons 5-7 were conducted because the corresponding human regions (exons 5-8) have been reported as being mutated most frequently in human colon cancers. Using these methods, we were unable to identify any p53 mutations in the highly conserved regions of exons 5-7 in either AOM- or DMH-induced colon adenocarcinomas. These data confirm that Ki-ras was mutated in most colon cancers in AOM- or DMH-treated rats but indicate that molecular alterations in the p53 gene, if they occur in this animal model, are different from most p53 mutations in human colon cancers.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Erdman SH,Wu HD,Hixson LJ,Ahnen DJ,Gerner EW

doi

10.1002/(sici)1098-2744(199707)19:2<137::aid-mc8>3

subject

Has Abstract

pub_date

1997-06-01 00:00:00

pages

137-44

issue

2

eissn

0899-1987

issn

1098-2744

pii

10.1002/(SICI)1098-2744(199707)19:2<137::AID-MC8>3

journal_volume

19

pub_type

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