Freshly prepared rat hepatocytes isolated by perfusion with collagenase were able to metabolize p.M concentrations of dimethylnitrosamine to a methylating agent. The methylation of hepatocyte DNA in this system was complete within 2 hr, and after this time, the content of O6-methylguanine in the DNA declined, showing that the repair system for this product was active in the isolated hepatocytes...

This report describes a new general assay for the microsomal oxidative dealkylation of nitrosamines. After precipitation of the microsomal proteins, aldehydes formed from nitrosamines are quantitated by high-pressure liquid chromatography as their 2,4-dinitrophenylhydrazones. This novel assay method offers some distinct advantages over the commonly used Nash re agent assay. Dimethylnitrosamine,...

The ability of certain species of bacteria and yeasts that usually contaminate fresh palm sap to induce the formation of the carcinogen dimethylnitrosamine from suitable precursors (trimethylamine, dimethylamine, nitrate, and nitrite) was investigated in vitro under neutral and acid pH conditions. In the incubation media containing cell suspensions of each species of test organism, namely, Aero...

1. N[14C]-Methyl-N-nitrosourea, [14C]dimethylnitrosamine, [14C]dimethyl sulphate and [14C]methyl methanesulphonate were injected into rats, and nucleic acids were isolated from several organs after various time-intervals. Radioactivity was detected in DNA and RNA, partly in major base components and partly as the methylated base, 7-methylguanine. 2. No 7-methylguanine was detected in liver DNA ...

The appearance of two cases of cirrhosis of the liver among three men working in the research laboratory of a large industrial undertaking led to suspicion becoming attached to dimethylnitrosamine (D.M.N.) as the causative agent. Dimethylnitrosamine had been introduced into the laboratory as a solvent about 10 months before the first case of cirrhosis was discovered. One of the men had died of ...

Hepatic fibrosis may ultimately result in organ failure and death, a reality compounded by the fact that most drugs for liver fibrosis appear to be effective only if given as a prophylactic or early treatment. In a dimethylnitrosamine-induced liver fibrotic model, aspartate aminotransferase/alanine aminotransferase levels could not precisely distinguish the differences between the initial stage...

Following i.p. injection of dimethylnitrosamine into male C57BL mice, synthesis of liver nuclear heterogeneous RNA was inhibited significantly, reaching approximately 20% of control within 2 hr of a dose of 40 mg/kg. Synthesis of nucleolar RNA was also inhibited, although to a smaller extent, reaching about 70% of control after the same treatment. These effects were observed both during RNA syn...