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Biomedical subjects

E Farber

Publications and source records attributed to E Farber.

At least 199 records · Page 11Linked to original sources

Evidence for ethylation of rat liver deoxyribonucleic acid after administration of ethionine.

1. Administration of a large dose (500mg/kg body wt.) of (3)H-labelled l-ethionine to rats resulted in the incorporation of a small amount of radioactivity into the liver DNA. Considerable evidence that this radioactivity was not due to contamination of the isolated DNA with labelled protein, RNA, S-adenosyl-l-ethionine or l-ethionine was obtained. 2. After acidic hydrolysis of the DNA isolated from the livers of rats treated with labelled l-ethionine, virtually all of the radioactivity present in the DNA was found in a fraction with similar chromatographic properties to 7-ethylguanine. 3. Treatment of rats with comparable doses of l-methionine did not lead to the formation of 7-methylguanine in the liver DNA. 4. These results are discussed in relation to the induction of liver tumours by ethionine.

Alkylation↗

Dissociation of effects on protein synthesis and ribosomes from membrane changes induced by carbon tetrachloride.

Pretreatment of rats with cycloheximide protects the liver against ribosome changes but not against alterations in the endoplasmic reticulum membrane induced by the administration of CCl(4), as observed both biochemically and ultrastructurally. Another inhibitor of protein synthesis, tenuazonic acid, has effects similar to cycloheximide. Neither compound has any apparent effect when given after the administration of CCl(4) at a time at which a major shift in ribosome distribution from polysomes to ribosome monomers or subunits has already occurred. Thus, it appears that the ribosomes are not susceptible to damage by CCl(4), or more probably an active metabolic derivative of CCl(4), when they are organized as polysomes but only when they are present as monomers or subunits. Also, unlike the situation with ethionine or puromycin, the damage to the protein synthetic system of the ribosomes induced in the liver by CCl(4) appears to be irreversible. In contrast to cycloheximide or tenuazonic acid, N,N'-diphenyl-p-phenylenediamine (DPPD) protects the liver against CCl(4)-induced changes in both ribosomes and endoplasmic reticulum. These observations suggest that the changes in the ribosome-protein synthetic system induced in the liver by treatment with CCl(4) are not the direct result of damage to the membranes of the endoplasmic reticulum but are either an indirect effect of such damage or are unrelated to it. These possibilities are discussed in terms of three proposed working hypotheses.

Animals↗