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Biomedical subjects

E Farber

Publications and source records attributed to E Farber.

At least 217 records · Page 12Linked to original sources

Studies on acute methionine toxicity. I. Nucleolar disaggregation in guinea pig hepatic cells with methionine or ethionine and its reversal with adenine.

The effects of methionine and ethionine on the fine structure of hepatic cell nucleoli of guinea pigs and rats were investigated. A single intraperitoneal injection of methionine into guinea pigs results in the disruption of nucleolonema as early as 2 hours after the injection. By 4 hours, nucleoli show complete fragmentation consisting of many small fragments and small remnants of nucleoli. Large aggregates of interchromatinic granules and condensation of chromatin appear in the nucleoplasm. These changes are remarkably similar to the lesions induced by ethionine in the liver of the rat or the guinea pig. The methionine-induced nuclear and nucleolar lesions persist up to 10 hours after the injection. The administration of adenine 4 hours after the methionine injection reverses the nucleolar lesions by 8 hours. The appearance of incompletely reconstructed nucleoli with twisted ropelike structures suggests a pattern of recovery very similar to the adenine-induced nucleolar reformation in ethionine-treated rats. Injecting methionine into rats induced no nucleolar abnormalities. It is suggested that the mechanism of nucleolar fragmentation induced by methionine or ethionine is related to the accumulation of S-adenosyl compounds with concomitant ATP deficiency in the liver.

Adenine↗

Growth in vitro of cells from hyperplastic nodules of liver induced by 2-fluorenylacetamide or aflatoxin B1.

Cell suspensions obtained from hyperplastic nodules induced in rat liver by either of the two hepatic carcinogens, 2-fluorenylacetamide or aflatoxin B(1), show growth when cultured in vitro. No growth of cells from liver adjacent to the hyperplastic nodules or from liver of control rats has been obtained so far under comparable conditions. Hepatocarcinoma cells induced by 2-fluorenylacetamide grow readily in vitro but behave differently. These findings suggest that some nonmalignant cells capable of growth in vitro arise during liver carcinogenesis prior to the appearance of unequivocal cancer. Cultures of such cells may offer new avenues for the study of liver carcinogenesis.

Aflatoxins↗

Reformation of nucleoli after ethione-induced fragmentation in the absence of significant protein synthesis.

The rat liver nucleolus, after fragmentation induced by ethionine treatment, has been found to undergo complete reformation by adenine in the presence of a dose of cycloheximide sufficient to cause inhibition of protein synthesis by 90-95%. In contrast, actinomycin D given along with adenine was followed by the appearance of a small compact mass containing only the fibrillar component with no evident granules. This structure resembled pseudonucleoli seen in the anucleolate mutant of Xenopus laevis or in certain early stages of amphibian oocytes. Actinomycin D administered 2 hr after adenine induced a segregation of the fibrillar and granular components of nucleoli similar to that induced in the normal nucleolus. The implications of these findings in relation to nucleolar organization are briefly discussed.

Adenine↗

Unusually high mitochondrial alpha glycerophosphate dehydrogenase activity in rat brown adipose tissue.

Brown adipose tissue of the rat has been found to have an unusually high activity of mitohondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) when assayed both by a histochemical staining procedure and by a quantitative biochemical method with isolated mitochondria. In contrast to succinic, glutamic, and beta-hydroxybutyrate dehydrogenases, all mitochondrial enzymes, the activity of alpha-GPD in brown fat was 10 times that in liver, more than 20 times that in white adipose tissue, and 9 times that in kidney. The soluble NAD-linked alpha-GPD was also higher in brown adipose tissue than in white adipose tissue, liver, or kidney, but the differences were much less marked. The possible importance of the high activity of mitochondrial alpha-GPD in the regulation of synthesis of esterified lipid and in thermogenesis in brown fat is discussed.

Adipose Tissue↗