DNA fragmentation by 2-nitropropane in rat tissues, and effects of the modulation of biotransformation processes

The occurrence and persistence of DNA fragmentation, as detected by the alkaline elution technique, have been studied in rats treated with single oral doses of the hepatocarcinogen 2-nitropropane (2-NP). A progressive increase of liver DNA fragmentation was observed at doses ranging from 0.5 to 8 mmol/kg; single strand breaks reached the maximum frequency 6 h after administration, and were partially reduced after 36 h. In contrast, DNA fragmentation was absent in lung, kidney, bone marrow and brain of rats given 8 mmol/kg. The role of cytochrome P-450 in the activation of 2-NP is indicated by the increase of liver DNA damage in rats pretreated with phenobarbital or beta-naphtoflavone, and by its reduction produced by methoxsalen. Both administration of GSH and GSH depletion did not result in clearcut modifications of the genotoxic effect of 2-NP for the liver.