Faculty Collaboration Database

Mutation in the p53 tumor suppressor gene in rat esophageal papillomas induced by N-nitrosomethylbenzylamine. Carcinogenesis 1996 Apr;17(4):625-30

Date

04/01/1996

Pubmed ID

8625469

DOI

10.1093/carcin/17.4.625

Scopus ID

2-s2.0-0029665106 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

Mutations in the p53 tumor suppressor gene have been implicated in the pathogenesis of a wide variety of human neoplasms. The location and types of p53 gene mutation can reflect exposure of humans to certain types carcinogenic agents. Much less is known about the role of p53 mutational inactivation in rodent tumors. Using both 'Hot' (radioactive) and 'Cold' (non-radioactive) single strand conformation polymorphism (SSCP) analyses, the present study of analyzed exons 5-8 and the exon-intron junction of the p53 gene from rat esophageal papillomas induces by N- nitrosomethylbenzylamine (NMBA) for mutations. Nine of 30 (30%) esophageal papillomas contained SSCP mobility shifts, principally within exons 5 and 7. These positive SSCP findings were further validated by direct DNA sequencing analysis. Eight of the nine mutations were G:C-->A:T transitions in codons 131, 149, 153, 242 (2), 243, 248, and the 5 end of intron 7. None of these G:C-->A:T mutations occurred at the CpG sites. The other mutation was a frameshift mutation in codon 176. The G:C-A:T transitions observed in this study are consistent with the documented formation of O(6)-methylguanine adducts in DNA N-nitroso compounds. These results suggest that point mutations of the p53 gene are involved in the development of approximately one-third of NMBA-induced rat esophageal papillomas. 'Hot' and 'Cold' SSCP methods were equally sensitive for the identification of mutations in the rat p53 gene.

Author List

Wang D, Weghorst CM, Calvert RJ, Stoner GD

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Carcinogens
DNA Primers
Dimethylnitrosamine
Esophageal Neoplasms
Exons
Genes, p53
Introns
Male
Molecular Sequence Data
Mutation
Papilloma
Polymorphism, Single-Stranded Conformational
Rats
Rats, Inbred F344