Alternative methods of selecting rat hepatocellular nodules resistant to 2-acetylaminofluorene.
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.
Semple-Roberts
E
E
Department of Pathology, University of Toronto, Ontario, Canada.
Hayes
M A
MA
Armstrong
D
D
Becker
R A
RA
Racz
W J
WJ
Farber
E
E
D015073:2-Acetylaminofluorene; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage; D004351:Drug Resistance; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014116:Toxicology / Q000379:methods*
D002273:Carcinogens; D015073:2-Acetylaminofluorene