HEPATOCELLULAR-CARCINOMA INDUCTION IN LEC RATS BY A LOW-DOSE OF 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE

A food-borne heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5-f]qui noxaline (MeIQx), induces hepatocellular carcinomas (HCCs) in F344 mal e rats at an incidence of 95%, when fed in the diet at 400 ppm for 61 weeks, In this study, the effect of a low dose of MeIQx was examined i n Long-Evans with cinnamon-like coat color (LEC) rats, which have a mu tation in Atp7b and suffer from hereditary hepatitis and HCCs, with hi gh levels of copper accumulation in the liver. Rats of the LEC and Lon g-Evens with agouti coat color (LEA) sibling lines were given a diet c ontaining 40 ppm MeIQx from the age of 23 weeks to 63 weeks, for a tot al administration period of 40 weeks. In LEC rats, HCCs were observed in 8/8 animals administered MeIQx, and 2/8 rats receiving a normal die t. The number of HCCs per rat (mean+/-SD) was 2.8+/-2.0 and 0.3+/-0.5, respectively. In the LEA rats, however, no tumors were induced by adm inistration of MeIQx, These results indicate that damaged liver associ ated with compensatory cell proliferation is much more susceptible to chemical hepatocarcinogens, including MeIQx, than the normal liver.