SCREENING FOR P53 GENE-MUTATIONS IN ARCHIVED TUMORS OF WORKERS OCCUPATIONALLY EXPOSED TO CARCINOGENS - EXAMPLES FROM ANALYSIS OF BLADDER-TUMORS

Point mutations in the p53 tumor suppressor gene are the most common g enetic alterations in human cancers. The nature and location of these mutations can be informative in assessing the importance of putative c arcinogenic agents. Potential associations between a given carcinogen and a specific mutation pattern can be substantiated when the exposure history of the patients is Known. while the past exposure to environm ental risk factors is often difficult to determine, documented occupat ional exposure to carcinogens presents a unique situation for evaluati ng this approach. Analysis usually involves working with paraffin-embe dded tissues, fixed under conditions suboptimal for genetic analysis a nd stored for many years, since frozen tissues are not available in su fficient numbers. The particular methodological problems encountered w ith fixed samples are discussed here, using as illustration an ongoing study of oncogene and tumor suppressor gene mutations in archived bla dder tumors of workers exposed to aromatic amines and nonexposed patie nts.