Sex and organ differences in oxidative DNA and RNA damage due to treatment of Sprague-Dawley rats with acetoxime or 2-nitropropane.
The hepatocarcinogens 2-nitropropane and acetoxime have previously been found to induce a specific and qualitatively identical pattern of base damage in rat liver DNA and RNA, including the induction of increased levels of 8-hydroxyguanine. Because both 2-nitropropane and acetoxime are weaker carcinogens in female rats than male rats, we examined the ability of these chemicals to induce this pattern of damage in liver and kidney nucleic acids of male and female Sprague-Dawley rats 6 and 18 h after administration. Significantly lower levels of 8-hydroxydeoxyguanosine, 8-hydroxyguanosine and other presumed modified nucleosides discernible by high-performance liquid chromatography with electrochemical detection were found in liver nucleic acids of female rats at both time points. In addition, minimal alteration of nucleic acids was observed in the kidney, which is not a target organ for the carcinogenicity of either 2-nitropropane (2-NP) or acetoxime (ACO). These results support the hypothesis that the specific DNA alterations observed are relevant to the hepatocarcinogenicity of 2-NP and ACO.
American Health Foundation, Valhalla, NY 10595.
N
N
Guo
C C
CC
Conaway
N S
NS
Hussain
E S
ES
Fiala
D000473:Alkanes / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009595:Nitroparaffins / Q000633:toxicity*; D009928:Organ Specificity; D010091:Oximes / Q000633:toxicity*; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D012313:RNA / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D000473:Alkanes; D002273:Carcinogens; D009595:Nitroparaffins; D010091:Oximes; D012313:RNA; D004247:DNA; C016617:2-nitropropane; C035911:acetoxime; D011407:Propane