Absence of DNA damage in liver of rats given high doses of cimetidine and sodium nitrite.
A correlation between cimetidine and gastric cancer has been suggested. Nitrosation of cimetidine in the presence of nitrite and HCl and mutagenic activity as well as DNA damage in mammalian cells displayed by nitrosocimetidine, as these phenomena occur in vitro, were the supporting hypothesis. Previous studies have shown that liver DNA damage was a well correlated index of potential carcinogenic activity of N-nitroso compounds and that such a damage was found after long-term simultaneous oral administration of aminopyrine and nitrite in rats. In this work, liver DNA fragmentation was investigated by three different techniques: DNA alkaline elution, DNA alkaline denaturation followed by hydroxylapatite chromatography and a new viscometric method markedly more sensitive than the above mentioned ones in detecting DNA damage. Evidence of DNA damage was not gained in any of the groups of rats treated with high single or successive oral daily doses of cimetidine (250 mg/kg) along with nitrite (80 mg/kg) in approximately equimolar amounts. Cimetidine and nitrite given alone were also ineffective. The lowering of gastric pH, obtained with fasting and histamine administration before giving cimetidine and nitrite combination in a single dose, did not favor the induction of liver DNA fragmentation neither in the above condition nor even when the amount of cimetidine was lowered to 125 mg/kg in order to obtain an approximately 2-fold molar amount of nitrite.
D000818:Animals; D002927:Cimetidine / Q000633:toxicity*; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D006146:Guanidines / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009573:Nitrites / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000633:toxicity*; D014783:Viscosity
D006146:Guanidines; D009573:Nitrites; D002927:Cimetidine; D004247:DNA; D012977:Sodium Nitrite