A microsomal membrane alteration following ethionine intoxication.

At both 4 and 24 hr after the administration of ethionine, female rats displayed a significant reduction in the RNA:pro tein ratio of liver microsomes. In this respect, ethionine behaved like many other hepatocarcinogens which induce ribosomal separation from the rough endoplasmic reticulum. This separation is usually brought about by the membrane, rather than ribosomal lesions. Using the disulfide-interchange activity of microsomal membranes we have shown that: (a) control membranes bound control ribosomes; (b) control membranes did not bind â€oe4-hr†• or â€oe24-hr†• ethionine ribosomes; (c) 4-hr ethionine-membranes would bind control ribosomes, but not 4-hr, ethionine ribosomes; and (d) 24-hr ethione membranes would not bind control ribosomes or ethionine ribosomes. These data indicate that separation of ribosomes from the endoplasmic reticulum 4 hr after the administration of ethionine is due to a ribosome lesion and not a membrane lesion. A membrane lesion occurs later and, 24 hr after the ethionine intoxication, both ribosomal and membrane lesions are present.