Use of genotypic selection to detect P53 codon 273 CGT>CTT transversion: application to an occupationally exposed population.
CGT>CTT transversion in codon 273 of the P53 tumor-suppressor gene is one of the major mutations detected in human tumors. Within an epidemiological framework, we investigated the use of a genotypic selection method to measure this point mutation. The allele-specific polymerase chain reaction (AS-PCR) that was developed was able to detect 10 mutant copies of the gene among a total of 5 x 10(5) wild-type copies. We used this assay to detect CGT>CTT transversions in buccal cell DNA of production workers (n=76) from a viscose factory exposed to carbon disulfide (amongst other pollutants) and in the DNA of non-exposed office workers (n=67). The mutation appeared more frequently in the exposed than in the non-exposed worker who were smokers. The results of the study indicate that occupational exposure results in a significant increase in P53 CGT>CTT transversions and more especially identified occupational exposure in combination with smoking as a significant risk factor for the mutation. We conclude that AS-PCR of the P53 273rd codon transversions is a suitable technique for studying the effects of occupational exposure.
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Département Environnement Santé Publique, Faculté de Médecine, Nancy, BP 184, 54505 Vandoeuvre, France. Thomas.Carton@medecine.uhp-nancy.fr
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Hartemann
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D000395:Air Pollutants, Occupational / Q000633:toxicity; D020137:Base Pair Mismatch; D002246:Carbon Disulfide / Q000633:toxicity*; D045744:Cell Line, Tumor; D002482:Cellulose; D002681:China / Q000453:epidemiology; D003062:Codon; D017931:DNA Primers; D016158:Genes, p53 / Q000187:drug effects* / Q000235:genetics; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D017720:Molecular Epidemiology / Q000379:methods*; D009061:Mouth Mucosa / Q000166:cytology; D016273:Occupational Exposure / Q000009:adverse effects*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012907:Smoking / Q000009:adverse effects; D013784:Textiles
D000395:Air Pollutants, Occupational; D003062:Codon; D017931:DNA Primers; D002482:Cellulose; C012024:rayon, purified; D002246:Carbon Disulfide