INFREQUENT ALTERATIONS OF THE P53 GENE IN RAT SKIN CANCERS INDUCED BYIONIZING-RADIATION

Radiation carcinogenesis almost certainly involves multiple genetic al terations, Identification of such genetic alterations would provide in formation to help understand better the molecular mechanism of radiati on carcinogenesis, The energy released by ionizing radiation has the p otential to produce DNA strand breaks, major gene deletions or rearran gements, and other base damages, Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in rad iation-induced rat skin cancers, Genomic DNA from a total of 33 rat sk in cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 g ene, An abnormal p53 restriction pattern was found in one of 16 cancer s induced by electron radiation and in one of nine cancers induced by neon ions, The genomic DNA from representative cancers, including the two with an abnormal restriction pattern, was further examined by poly merase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene, The results showed that one restriction fragment len gth polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between ex ons 2-8, while none of the other cancers showed sequence changes, Our results indicate that the alterations in the critical binding region o f the p53 gene are infrequent in rat skin cancers induced by either el ectron or neon ion radiation.