INDUCTION BY CARCINOGENS AND CHEMOPREVENTION BY N-ACETYLCYSTEINE OF ADDUCTS TO MITOCHONDRIAL-DNA IN RAT ORGANS

Damage to mitochondrial DNA (mtDNA) has been postulated to be associat ed with aging, cancer, and other chronic degenerative diseases which a re the predominant causes of death in the population, We used molecula r dosimetry techniques, i.e., P-32 postlabeling and synchronous fluore scence spectrophotometry, in order to evaluate the formation of adduct s to both mtDNA and nuclear DNA (nDNA) in different organs of rats exp osed to genotoxic carcinogens, Adducts to mtDNA were detected followin g administration of benzo(a)pyrene i.p. or 2-acetylaminofluorene by ga vage as well as following exposure of animals to cigarette smoke, mtDN A adduct levels were consistently higher than those to nDNA in the sam e cells, and qualitative differences were also pointed out in the case of the aromatic amine. The oral administration of the thiol N-acetylc ysteine, one of the most promising cancer chemopreventive agents endow ed with nucleophilic and antioxidant properties, produced a significan t decrease of mtDNA adducts in the liver of 2-acetylaminofluorene-trea ted rats and, sharply, in the lung and liver of rats exposed to cigare tte smoke.