Damage and repair of rat liver DNA by simultaneous oral administration of amines and nitrite.
The effect of simultaneous oral administration of dimethylamine or aminopyrine and sodium nitrite on the damage and repair of rat liver DNA was studied by the use of centrifugation in alkaline sucrose gradient. Fragmentation of the intact DNA was observed significantly shortly after combined treatment with aminopyrine and nitrite when no liver necrosis occurred yet and the damaged DNA at the lower dosage level of aminopyrine with nitrite was found to be repaired in contrast to the increased activity of serum aminotransferase. The lowest effective dose on DNA damage at 2 hr after administration was about 40 mg/kg of aminopyrine and 80 mg/kg of sodium nitrite. This effect was equal to that caused by single oral administration of 2 to 10 mg/kg of dimethylnitrosamine, while dimethylamine at 160 or 320 mg/kg together with 80 mg/kg of sodium nitrite produced no pronounced DNA damage. The significant damage of rat liver DNA by aminopyrine and nitrite correlates well with the easier nitrosation of aminopyrine and the occurrence of high incidence of malignant liver tumors in rats fed aminopyrine together with nitrite already reported by Lijinsky.
D000410:Alanine Transaminase / Q000097:blood; D000632:Aminopyrine / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D004123:Dimethylamines / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009573:Nitrites / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D004123:Dimethylamines; D009573:Nitrites; D000632:Aminopyrine; D004247:DNA; D000410:Alanine Transaminase; D013936:Thymidine