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.