Propane 2-nitronate is more rapidly denitrified and is more genotoxic than 2-nitropropane in cultured rat hepatoma cells.
We have investigated the importance of nitronate formation from 2-nitropropane (2-NP) for the oxidative metabolism and the genotoxicity of 2-NP in 2sFou rat hepatoma cells. Treatment of the cells with 2-NP for up to 3 h resulted in the time-dependent appearance of nitrite in the culture medium and in a weak induction of DNA repair synthesis. Both nitrite formation and repair induction were markedly enhanced in cells exposed to the anionic form of 2-NP, propane 2-nitronate. These observations suggest that propane 2-nitronate, rather than 2-NP itself, is oxidized by the liver cells to yield a DNA-damaging product. The results also indicate that the nitro/nitronate equilibration in intact liver cells is slow, suggesting that nitronate formation represents the rate-limiting step in the metabolic activation of 2-NP.
Dalke
C
C
GSF-Institut für Toxikologie, Neuherberg, Germany.
Andrae
U
U
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009595:Nitroparaffins / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction; D011407:Propane / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D051381:Rats
D009595:Nitroparaffins; C069720:propane-2-nitronate; D004247:DNA; C016617:2-nitropropane; D011407:Propane