P53 MUTATIONS AT A-T BASE-PAIRS IN ANGIOSARCOMAS OF VINYL CHLORIDE-EXPOSED FACTORY-WORKERS

Mutations in the p53 tumor suppressor gene are commonly found in the m ajor human cancers and the mutational spectrum in some cancer types is consistent with the genotoxic effects of the associated envirommental risk factors. Thus far there is little information on p53 mutations i n cancers of factory workers with a history of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride causes liver an giosarcomas (ASL) and also increases the risk of several other cancers . Loss of p53 function in osteo- and fibrosarcomas can occur by two di fferent mechanisms, p53 mutation and amplification of the MDM2 gene. W e examined tumors from five vinyl chloride-exposed patients, four with ASL and one with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene amplification or p53 mutation in exons 5-8. Amplificat ion of MDM2 was not found, but in two of the angiosarcomas an A:T to T :A missense mutation was detected. p53 sequence analysis of vinyl chlo ride associated cancers may provide valuable information on the relati onship between carcinogen exposure and DNA damage in cancer-related ge nes.