Alternative methods of selecting rat hepatocellular noduli resistant to 2‐acetylaminofluorene

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Abstract
Dietary 2‐acetylaminofluorene (2‐AAF) coupled with a stimulus for cell proliferation such as a 2/3 partial hepatectomy (PH) or a necrotizing dose of carbon tetrachloride is frequently employed to generate nodules of resistant (“initiated”) rat hepatocytes. This regimen is a useful model for experimental analysis of alterations in hepatocytes during carcinogenesis, and also as an assay for initiation by various carcinogens. Because of the decreasing availability of carcinogen‐containing diets from commercial sources, we have developed alternative methods of 2‐AAF administration to generate nodules in rats initiated with N‐nitrosodiethylamine. This study compared the nodule‐selecting and cancer‐promoting efficacy of 2‐AAF administered by the Solt‐Farber procedure (0.02% in diet for 2 weeks) with 2‐AAF administered by gavage, as a suspension in 1% aqueous carboxymethyl‐ cellulose (CMC). Three or 4 daily administrations of 2‐AAF by gavage (20 mg/kg/day) followed by PH on day 4 were equivalent to the dietary regimen in generating early resistant nodules, late persistent nodules and hepatocellular carcinomas. These regimens were similar to the dietary regimen of 2‐AAF in inhibiting virtually all normal hepatocyte proliferation. These regimens permit control over the duration and level of 2‐AAF exposure and the resulting size of selected nodules.