Modifying effects of chemicals on the development of liver preneoplastic placental glutathione S-transferase positive foci in analbuminemic and Sprague-Dawley rats.

Nagase analbuminemic rats (NARs) were compared to the Sprague-Dawley (SD) stock in a medium-term assay system for hepatocarcinogenesis regarding their susceptibilities to the influence of chemicals on the development of glutathione S-transferase, placental form, positive (GST-P+) foci. Two weeks after initiation with diethylnitrosamine (DEN), the animals were exposed alternatively to 0.06% 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB), 50 ppm DEN, 0.25% ethionine, 1% clofibrate, and 1% butylated hydroxyanisole (BHA) for a 6-wk period. Adequate controls included groups only initiated with DEN or treated with each test compound alone. For evaluation of the modifying potential of the chemicals, indices were generated by using the mean values obtained for number and area of GST-P+ foci after each treatment. Comparison between these indices suggests that SD rats were relatively more sensitive than NARs to the modifying effects of complete carcinogens (3'-Me-DAB and DEN). The strains were similarly-susceptible to the promoting influence of ethionine, a nongenotoxic carcinogen. The inhibitory influence of BHA was more intense in NARs, whereas in both strains clofibrate was associated to similarly reduced values for number and area of GST-P+ foci. The degree of susceptibility of each strain to the modifying influence of chemicals on foci development depended on the chemical agent investigated.