Effect of a p53 codon 237 mutation on X-ray induced HPRT mutations

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To determine the influence of mutant p53 on HPRT mutations induced by ionizing radiation, we irradiated human lymphoblastoid cell lines TK6 (wild-type p53) and WI-L2-NS (mutant p53 at codon 237) with X-rays. We applied multiplex PCR analysis for independent mutants arising spontaneously or induced by X-ray exposure. X-rays enhanced the HPRT mutation frequency, yielding values that were 6 times the spontaneous level in TK6 and 6.8 times that level in WI-L2-NS. Point mutations (all exon regions amplified by PCR), which comprised the major portion of spontaneous mutations (60〜80 %) in both cell lines, were decreased by X-ray irradiation. In contrast, the proportion of complete deletions (no exon region amplified) was increased. These tendencies of decrease and increase after irradiation were the same as those reported by Phillips et al. (1995) but not statistically proved by chi-2 test. Although such test also can not show the statistic significance in the following differences, the proportion of partial deletions (some exon regions amplified) increased in TK6 but decreased in WI-L2-NS, reflecting the relatively high spontaneous level (29%) of such mutations in WI-L2-NS relative to the level (8%) in TK6. The high level of spontaneous partial deletions in p53 mutant cells was primarily attributable to a frequent (6/8) specific event-deletion of exons 2 to 5. X-ray reduced that frequency to a more ordinary level (1/8). As reported by Phillips et al. (1995), we also did not detect any effect of the codon 237 of p53 mutation on the distribution of point mutations, partial deletions, or complete deletions in X-ray-induced HPRT mutants.
日本環境変異原学会の論文
2002-05-31

Effect of a p53 codon 237 mutation on X-ray induced HPRT mutations

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