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The Effect of L-Asparaginase on Mitotic Activity during N-2-Fluorenylacetamide Hepatocarcinogenesis: Subpopulations of Nodular Cells¹

Department of Pathology, New York University School of Medicine, New York, New York 10016

Normal rat liver hepatocytes and the hepatocytes of hepatic nodules induced by N-2-fluorenylacetamide respond to 70% hepatectomy with vigorous mitotic activity. The administration of L-asparaginase at the time of operation delays the mitotic cycle of every normal hepatocyte by 10 to 12 hr. When L-asparaginase was administered to rats which had received N-2-fluorenylacetamide, an 80% inhibition of mitotic activity of the hepatocytes of the nodules occurred. However, aggregates of cells resistant to the effect of the enzymes were noted in a number of nodules. These resistant cells represent a metabolic subpopulation within the hyperplastic nodule.

¹ Supported by American Cancer Society Grant E-355C.

² Career Scientist, Health Research Council of the City of New York.

³ USPHS Fellow in Experimental Pathology.

Received 8/26/70. Accepted 10/ 6/70.