Alteration of Hepatocytes by Subcarcinogenic Exposure to /V-2-Fluoreny lacetamide1

These experiments examined the effects of a single, subcarcinogenic dose of dimethylnitrosamine or 7V-hydroxyfluorenylacetamide when administered after a subcarcino genic dietary regimen of yV-2-fluorenylacetamide. Control rats that received either carcinogen diet alone or a single dose of carcinogen demonstrated neither hepatic nodules nor hepatocellular carcinomas. Those animals that received dimethylnitrosamine subsequent to carcinogen diet demon strated many persistent hepatic nodules and 100% hepato cellular carcinomas. These data support the concept that the nodules produced by subcarcinogenic ingestion of 7V-2-fluorenylacetamide are not composed simply of normal hepatocytes undergoing compensatory regeneration but consist of cells that have been altered by the carcinogen. One manifestation of this alteration is an increased susceptibility to further carcino genic evolution.