Carcinogen daily dose-dependence of the biological features and development rate of hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene in the rat.

Differences in biological features and the rate development of hepatocellular carcinomas (HCCs) induced with various daily doses of 3'-methyl-4-dimethylaminoazobenzene were investigated. Male Donryu rats at 21 days old were fed the carcinogen at concentrations ranging from 50 to 600 ppm in the diet continuously, or 600 ppm for 3 weeks followed by a dietary promoting regimen of 500 ppm phenobarbital. Large (> or = 10 mm) HCCs were monitored and the histological features and alpha-fetoprotein (AFP) production analysed. High doses of the carcinogen predominantly induced HCCs of high grade malignancy with AFP production in a short latent period whereas lower doses and the initiation-promotion protocol were primarily associated with low grade HCCs lacking AFP production and developing after long latent periods. Thus the experimental results clearly document that biological features of neoplasms, viewed as a spectrum, may markedly differ according to the daily dose of the carcinogen applied.