The possible discrepancy between the dose level required for promoting action (when given after the initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen) of hepatic promoters were investigated in an attempt to obtain a “practical” threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichlorethane (DDT) were used as promoters and 3‘-methyl-4-(dimethylamino)-azobenzene (3’-Me-DAB) was used as the carcinogen. Male weanling rats were treated with either 600 ppm 3‘-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5–500 ppm), or the animals were treated with a low dose (100 ppm) of 3’-Me-DAB plus a promoter at various dose levels (20–500 ppm). The effects of promoters were measured by scoring size and number of enzyme-altered islands (EAIs) at 12 and 24 weeks of age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10–500 ppm and 20–500 ppm, respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced carcinogenesis at all the dose levels tested, in contrast with the inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens.
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