SUSCEPTIBILITY OF P53-DEFICIENT MICE TO INDUCTION OF MESOTHELIOMA BY CROCIDOLITE ASBESTOS FIBERS

Exposure oi mesothelial cells to asbestos fibers in vitro has been sho wn to induce DNA damage mediated by oxidants. An early cellular respon se to DNA damage is increased expression of the p53 protein. This prot ein induces transcription of genes that activate cell cycle checkpoint s or induce apoptosis. A murine mesothelial cell line that spontaneous ly acquired a point mutation in the p53 gene shows increased sensitivi ty to DNA damage induced by crocidolite asbestos fibers. It is hypothe sized that p53-deficient mice will show increased sensitivity to the g enotoxic effects of asbestos and accelerated development oi malignant mesothelicmas.