ASBESTOS INCREASES MAMMALIAN AP-ENDONUCLEASE GENE-EXPRESSION, PROTEIN-LEVELS, AND ENZYME-ACTIVITY IN MESOTHELIAL CELLS

Only two DNA repair enzymes, DNA polymerase beta and O-6-methylguanine -DNA methyltransferase, have been shown to be inducible in mammalian c ells by genotoxic agents, We show here that crocidolite asbestos induc es the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothel ioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 mu g/cm(2) s ignificantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleur al mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle, Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus bu t also in mitochondria. Our data are the first to demonstrate the indu cibility of AP-endonuclease by a human class I carcinogen associated w ith oxidant stress in normal cells of the lung.