INHIBITION BY N-ACETYLCYSTEINE OF CARCINOGEN-DNA ADDUCTS IN THE TRACHEAL EPITHELIUM OF RATS EXPOSED TO CIGARETTE-SMOKE

The ability of the aminothiol N-acetylcysteine (NAC) to prevent the fo rmation of carcinogen-DNA adducts in tracheal epithelial cells was inv estigated in Sprague-Dawley rats exposed whole-body to mainstream ciga rette smoke for either 40 or 100 consecutive days. P-32-Postlabelling analyses showed the occurrence of DNA adducts (12.49 adducts/10(8) nuc leotides) after 40 days of exposure, with a trend to formation of char acteristic diagonal radioactive zones. Total adduct levels were not fu rther enhanced after 100 days of exposure to smoke, although significa nt changes occurred in the amounts of individual adducts. NAC, given b y gavage in the 40 day study and in drinking water in the 100 day stud y, significantly inhibited the formation of smoke-related carcinogen-D NA adducts in the tracheal epithelium, to such an extent that adduct l evels were not significantly higher than those detected in sham-expose d control rats. Together with a variety of other molecular, clastogeni city, metabolic, cytological and histopathological end-points investig ated in rodents and with the preliminary evidence arising from a study in humans, these results document the considerable efficacy of oral N AC in inhibiting smoke-related carcinogen-DNA adducts.