5 % respectively of the total (whole homogenate) activity; the postmitochondrial (1OOOOg) supernatant contained the whole of the activity. Further, on resuspending the microsomal fraction in the cell sap, all the dimethylnitrosamine demethylase activity was restored. The kinetics of dimethylnitrosamine demethylase were investigated in hepatic 1OOOOg supernatants over a substrate concentration r...

1. Administration of a single dose of dimethylnitrosamine to rats temporarily fed on a protein-deficient diet causes a high incidence of kidney tumours. The effect of such a dose of dimethylnitrosamine (40mg/kg body wt.) on metabolism of nucleic acids and protein in rat liver and kidneys was examined during the week immediately after administration. 2. Incorporation of [(14)C]leucine and [(14)C...

Nitrosamines are a potent and versatile group of carcinogens and by the generally accepted mechanisms of their carcinogenicity require metabolic transformation to alkylating agents or carbonium ions before they become biologically active (Hultin et al., 1960; Heath, 1962). Metabolic studies of dimethylnitrosamine in the rat have shown that it was readily metabolized to CO, (Magee, 1956) and tha...

DNA, isolated from two samples of human liver obtained from a suspected dimethylnitrosamine poisoning, contained 1363 to 1373 micromol of 7-methylguanine per mol of guanine and 273 to 317 micromol of O6-methylguanine per mol of guanine. Liver and kidney DNA obtained from unrelated cases contained no detectable methylated purines. From the DNA methylation levels, it is estimated that the dimethy...

Exposure to nitrosamines may be the occupational risk factor for liver cirrhosis. 2-(Allylthio)pyrazine, a chemopreventive agent, inhibits CYP2E1 and induces phase II enzymes. We examined the effects of 2-(allylthio)pyrazine on hepatic fibrosis, a prepathologic state of cirrhosis, and on the expression of transforming growth factor-beta1 induced by dimethylnitrosamine. Treatment of rats with di...

(Fig. 1 ) . These compounds also had some effect on the proportion of the 14C recovered in the urine. N-Nitrosopyrrolidine inhibits the metabolism of dimethylnitrosamine to formaldehyde by rat liver l O O O O g supernatant. The form of the dependence of the rate of dimethylnitrosamine metabolism to formaldehyde on inhibitor concentration (shown in Fig. 2) suggests that there is a competitive ef...

Dimethylnitrosamine is a potent hepatocarcinogen in a number of animal species including the rat (Magee & Barnes, 1956). Previous investigations into the hepatic metabolism of dimethylnitrosamine in vitro have shown that this compound is metabolized to formaldehyde, a process requiring NADPH and molecular oxygen (Magee & Vandekar, 1958). The requirement for these two cofactors has led to the su...

1. Groups of rats were given one dose of the carcinogen dimethylnitrosamine by gastric intubation. The dose was varied between 10mg/kg body wt. and 1 microgram/kg body wt. 2. The dose was rapidly absorbed. 3. The methylation of liver DNA resulting from the administration of this carcinogen was proportional to dose. This suggests that small doses are absorbed from the gut with no more loss than ...

1. The concentrations of the nicotinamide-adenine dinucleotides in rat liver have been determined at intervals during the period 1-24hr. after feeding adult female rats with dimethylnitrosamine or thioacetamide. 2. The administration of dimethylnitrosamine resulted in a rapid decrease in the sum of NAD+NADH(2). This sum was decreased by 40% 3hr. after dosing. 3. Dimethylnitrosamine administrati...

Of 38 pure cultures of microorganisms tested, only one, Pseudomonas stutzeri, was capable of forming dimethylnitrosamine from dimethylamine and nitrite during growth. Resting cells of P. stutzeri, Cryptococcus terreus, Escherichia coli, and Xanthomonas campestris formed dimethylnitrosamine, although no nitrosamine was found in growing cultures of the latter three organisms. No nitrosamine was p...