Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis

Abstract

Possible discrepancy between the dose level required for promoting action, when given after 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 dichlorophenyltrichloroethane (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 600 p.p.m. 3′-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5–500 p.p.m.), or the animals were treated with a low dose (100 p.p.m.) of 3′-Me-DAB plus a promoter at various dose levels (20–500 p.p.m.). The effects of promoters were measured by scoring size and number of enzyme-altered islands at weeks 12 and 24 of rat age. The promoting effect of PB and DDT was demonstrated in dosedependent fashion, in the dose range of 10–500 p.p.m. and 20–500 p.p.m., respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced the carcinogenesis at all the dose levels tested, quite in contrast with their inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens.