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-Fetoprotein in Toxic Liver Injury¹

The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, Washington 98195 [E. A. S., M. K.], and the Department of Pathology, University of California, San Diego Campus, La Jolla, California 92037 [S. S.]

The temporal sequence of -fetoprotein appearance in serum was determined in both necrogenic and nonnecrogenic liver injury. Ethionine, thioacetamide, and CCI₄ were used to intoxicate male and female rats for evaluating serum enzyme levels, mitotic indices, and morphological reflections of impairment. Thioacetamide- and CCI₄-induced cell death preceded the mitotic wave in residual hepatocytes, and, in the case of both agents, this intoxicant-mediated necrosis preceded the emergence of -fetoprotein. Yet, although there was no evidence of either cell destruction or significant mitotic activity in ethionine-poisoned animals, serum -fetoprotein levels progressively increased. Thus the temporal sequence of -fetoprotein synthesis and/or release and cellular reorganization for regeneration suggests that reappearance of the protein macromolecule is an expression of the altered phenotype observed during the "step-down" phase of liver regeneration.

¹ Supported in part by USPHS Grants AM 08686 and CA 13600 and by Contract CP-33403-31.

² Present address: Department of Pathology, University of California School of Medicine, San Francisco, Calif. 94143. To whom requests for reprints should be addressed.

Received 5/12/76. Accepted 9/10/76.