To determine whether the chronic consumption of ethanol was capable of enhancing the hepatocarcinogenic activity of diethylnitrosamine per se, or through the accentuation of a methyl deficiency, two groups (A and B) of Sprague-Dawley female rats were fed for 10 months either a 20% casein basal diet marginally deficient in methyl, or the same diet supplemented with choline (1 gm per 100 gm) and folic acid (0.54 mg per 100 gm). Both groups were offered a drinking ethanol solution, while two other nonalcohol control groups (C and D) were isocalorically pair-fed to Groups A and B, and received diets in which the alcohol consumed by the corresponding groups was replaced by isocaloric amounts of sucrose. A baseline nonalcohol Group E, isocalorically pair-fed to Group A, received the intact basal diet of Group A and water. One day before the initiation of the experiment, and again 2 months later, all rats from the five groups were injected with a single i.p. dose of diethylnitrosamine (100 mg per kg). The growth attained by all groups was statistically similar. Hepatic triglycerides in Group A were significantly higher than in all the other groups. While in Group A primary hepatocellular carcinomas and renal tumors were encountered at the end of the experiment in 3 of 6 and in 2 of 6 rats, respectively, no malignancies were observed in any of the other groups. These results indicate that chronic ethanol consumption enhances the hepatocarcinogenic and renal tumorigenic activity of diethylnitrosamine, and strongly suggest that this action is mediated through the accentuation of methyl deficiency.

An enantiomerically pure (1Z,3E)-sulfinyl diene exhibited a high degree of facial selectivity (α:β = 16:1) upon complexation to an iron(0) tricarbonyl fragment, producing a [η4-(1Z)-sulfinyl diene]iron(0) tricarbonyl complex (2; 80%). The iron(0)−dienal complex derived from 2 can undergo a highly diastereoselective allylation with allyltri-n-butylstannane and BF3·Et2O (diastereomer ratio 95:5); the absolute stereochemistry of the homoallylic alcohol product (4) was established by X-ray crystallography.

Seven groups of female Sprague-Dawley rats (approximately 200 gm initial body weight) were injected i.p. with a single subcarcinogenic dose of diethylnitrosamine (40 mg per kg body weight) between 8 to 10 hr after partial hepatectomy, and after a recovery period of 3 weeks (herein called induction stage) received 0.05% phenobarbital in the diet for the rest of the experiment (promotion stage). The rats were fed a 20% casein-based diet containing 0.16 ppm of selenium or the same diet supplemented with 4 or 6 ppm of selenium as sodium selenite. The effects of these three dietary regimens were tested when administered 9 to 11 days before and during induction, 1 week before and during promotion or during the entire experiment. Pair-feeding conditions were used to minimize influences due to differences in food intake and growth. Despite similarities in food intakes, the growth rates in groups receiving the 6 ppm-selenium diet during promotion or during the entire experiment were in general significantly lower than in rats fed the 4 ppm-selenium diet or the 0.16 ppm-selenium basal diet. Survival rates were also significantly reduced in rats fed the 4 and 6 ppm-selenium diets during promotion or during the entire experiment. In rats killed at the 19th week for interim assessment of the experiment's progress, the stereologically analyzed numerical and volumetric densities of hepatic premalignant hyperplastic nodules did not differ significantly between groups. All the remaining rats were killed at the 46th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Four groups of weanling male Wistar rats (Groups A-D) received diethylnitrosamine (DEN, 40 ppm) in their drinking water for four weeks; after a recovery period of two weeks, they received (for the rest of the experiment) phenobarbital (PB, 500 ppm) added to a Torula yeast-based diet containing 0.17 ppm of selenium. Dietary selenium (2 ppm), as sodium selenite, was given to Group B one week before and during DEN treatment, to Group C one week before and during PB treatment, and to Group D during the entire experiment. Groups A and E received the unsupplemented diet, whereas Group E was not treated with DEN or PB. Pair-feeding conditions were used to minimize possible influences of differences in food intake and growth. Rats were killed at the 19th and 24th weeks after the experiment began. No significant differences were found in food and fluid intakes or in growth rates among the groups. Livers in Group E were histologically normal, whereas preneoplastic and neoplastic lesions were found in all other groups. In rats killed at the 19th and 24th weeks, the numerical and the volumetric densities of preneoplastic lesions did not differ significantly between all the groups. Similarly, the incidence of hepatocellular carcinomas only detected at 24 weeks was not significantly different between the groups. These results indicated that in this particular model of hepatocarcinogenesis, the dietary supplementation of 2 ppm of selenium did not modify the development of preneoplasia and carcinomas.