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1 Departments of Pathology, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts
C14 and Cl36 from carbon tetrachloride are incorporated into lipids, proteins and acid-soluble constituents of livers of adult rats within 2 hr following the oral administration of this chlorocarbon. Upon isolation of cytoplasmic organelles, both isotopes preferentially label microsomal lipids. Protein labeling with C14 occurs at a single amino acid locus tentatively identified as methionine. Although the pattern of binding of C14 from carbon tetrachloride into chemical constituents of liver in newborn rats is similar to that of adult rats, the amount bound per gram of newborn liver is reduced to less than half. Administration of a sublethal dose of carrier carbon tetrachloride together with C14Cl4 increases the relative amounts of chlorocarbon carbon bound in protein and recovered from the cell sap. Bicarbonate and phosgene fail to label those chemical constituents of liver lipids and proteins labeled by carbon tetrachloride. The pattern of labeling of cytoplasmic constituents of liver with carbon and chlorine from carbon tetrachloride supports the hypothesis that carbon tetrachloride is toxic to liver cells by virtue of chemical attack of its cleavage products on the lipid and protein components of the endoplasmic reticulum.
Submitted on January 14, 1966
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