Oxidative DNA and RNA damage in rat liver due to acetoxime: similarity to effects of 2-nitropropane.
Acetoxime (ACO) and 2-nitropropane (2-NP), both industrially important chemicals and known hepatocarcinogens in rats, induced increased levels of 8-hydroxy-guanine in liver DNA and RNA of male Sprague-Dawley and F344 rats after either oral or i.p. administration. Both compounds also produced qualitatively the same patterns of other apparent modifications of liver DNA and RNA nucleosides, discernible by HPLC with electrochemical detection. Six hours after administration, the effects of 2-NP on liver nucleic acids were more pronounced in F344 rats than in Sprague-Dawley rats, suggesting that 2-NP may prove to be a stronger carcinogen in the F344 strain. The effects of ACO, a weaker carcinogen than 2-NP, were less than those of the nitroalkane in both rat strains. These results suggest that the hepatocarcinogenicity of ACO, like that of 2-NP, may depend on increased generation of reactive oxygen species capable of producing DNA and RNA base damage in rat liver. In addition, the data support the hypothesis that the hepatocarcinogenicity of ACO depends on its partial in vivo N-oxidation to 2-NP.
Hussain
N S
NS
American Health Foundation, Valhalla, NY 10595.
Conaway
C C
CC
Guo
N
N
Asaad
W
W
Fiala
E S
ES
D000284:Administration, Oral; D000473:Alkanes / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D003853:Deoxyribonucleosides / Q000302:isolation & purification; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009595:Nitroparaffins / Q000633:toxicity*; D009705:Nucleosides / Q000302:isolation & purification; D010091:Oximes / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D012313:RNA / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012997:Solvents
D000473:Alkanes; D003853:Deoxyribonucleosides; D009595:Nitroparaffins; D009705:Nucleosides; D010091:Oximes; D012997:Solvents; D012313:RNA; D004247:DNA; C016617:2-nitropropane; C035911:acetoxime; D011407:Propane