FIBER-SPECIFIC MOLECULAR-FEATURES OF TUMORS INDUCED IN RAT PERITONEUM

Molecular markers such as mutational spectra or mRNA expression patter ns may give some indication of the mechanisms of carcinogenesis induce d by fibers and other carcinogens. In our study, tumors were induced b y application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. Wit h both assays we found typical features depending on the type of carci nogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substit ution within one of the functional domains of the tumor suppressor pro tein. Therefore, these mutations seem to be of biological relevance;or tumor progression and indicate a difference in the carcinogenesis reg arding the type of the carcinogenic substance. An additional specifici ty of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expr essed in human mesothelial and mesothelioma cells. A relatively high a mount of WT1 mRNA was measured by quantitative competitive reverse tra nscription-polymerase using RNA extracted from crocidolite-induced tum ors. However, WT1 seems to be expressed on a rather low level in rumor s induced by B[a]P.