Use of genotypic selection to detect P53 codon 273 CGT>CTT transversion: Application to an occupationally exposed population

Abstract

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 5×10 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.