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p53 gene mutation analysis in tumors of patients exposed to alpha-particles.

Abstract：

:The p53 gene was examined for point mutations in archived, alpha-radiation-associated lung and liver cancers. Lung tumors of 50 uranium miners in Germany were screened by restriction fragment length analysis for the putative hotspot mutation at codon 249 (Arg-->Met) previously detected in a significant fraction of miners from the Colorado Plateau, USA. This mutation has been proposed as a marker of radon exposure. None of the tumors we examined harbored the hotspot mutation. Five of the 50 tumors, however, did indeed harbor exon 7 mutations, as determined by subsequent mutation analysis of exon 7. These mutations were dispersed among various codons and may be attributable to heavy tobacco smoking in this cohort. In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent. We propose that if the p53 tumor suppressor gene is a target for the carcinogenic action of alpha-particle radiation, loss of suppressor function may occur preferentially by mechanisms such as intrachromosomal deletions, rather than by base substitution mutations.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Hollstein M,Bartsch H,Wesch H,Kure EH,Mustonen R,Mühlbauer KR,Spiethoff A,Wegener K,Wiethege T,Müller KM

doi

10.1093/carcin/18.3.511

subject

Has Abstract

pub_date

1997-03-01 00:00:00

pages

511-6

issue

3

eissn

0143-3334

issn

1460-2180

journal_volume

18

pub_type

杂志文章

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