title: DNA fragmentation by 2-nitropropane in rat tissues, and effects of the modulation of biotransformation processes.
abstract: 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.
authors.affiliation: Institute of Pharmacology, University of Genoa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Robbiano
authors.forename: F
authors.initials: F
authors.lastname: Mattioli
authors.forename: G
authors.initials: G
authors.lastname: Brambilla
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009595:Nitroparaffins / Q000378:metabolism / Q000633:toxicity*; D009928:Organ Specificity; D010634:Phenobarbital / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
chemical_list: D001571:Benzoflavones; D002273:Carcinogens; D009595:Nitroparaffins; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; C016617:2-nitropropane; D011407:Propane; D010634:Phenobarbital