Suppressive effect of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats.
In order to elucidate the mechanism by which molybdenum prevents the carcinogenesis of N-nitroso compounds, the effects of Na2MoO4-pretreatment on N-nitrosodiethylamine (NDEA)-induced DNA strand breaks, fluctuation in cation contents and lipid peroxidation levels in rat liver were examined. Male Wistar rats weighing 170-190 g were pretreated with Na2MoO4 (1.24 mmol/kg body weight, i.p., once a day) for 3 d and on day 4, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). Three days after exposure to NDEA, the nitroso compound caused DNA strand breaks and disrupted potassium (K) and calcium (Ca) metabolism in the liver but did not affect lipid peroxidation levels. Na2MoO4-pretreatment prevented both NDEA-induced DNA damage and disruption of the metabolism of those cations but rather enhanced lipid peroxidation. These results suggest that Mo prevented NDEA-induced DNA damage by preventing disruption of intracellular Ca metabolism while stimulating the metabolism of the nitroso compound via a nontoxic pathway.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Tajima
K
K
Emi
N
N
Hara
A
A
Suzuki
K T
KT
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008982:Molybdenum / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D004052:Diethylnitrosamine; D008982:Molybdenum; D004247:DNA; D011188:Potassium; D002118:Calcium