Medium-term rat liver bioassay for rapid detection of carcinogens and modifiers of hepatocarcinogenesis

For rapid detection of carcinogenic agents, a medium-term liver bioassay has been established in our laboratory using preneoplastic glutathione S-transferase placental form (GST-P) positive foci in the rat liver as endpoint marker lesions. A total of 237 compounds have so far been tested in this system and the results compared with reported Salmonella/microsome and long-term carcinogenicity test findings. The positive rate was found to be extremely high, 97% (28 of 29 compounds) for genotoxic hepatocarcinogens; and satisfactory, 86% (23 of 27 chemicals) for nongenotoxic ones. The positive rate for carcinogens targeting organs other than the liver, however, is relatively low (24%). Malathion and vinclozolin proved positive, although both have been reported to be noncarcinogenic in rats and mice. Those chemicals which exerted positive results in this system might be hepatopromoting agents even if hepatocarcinogenicity has not been established. Five of the six false-negative hepatocarcinogens could be categorized as peroxisome proliferators. In addition, a number of inhibitory agents for GST-P-positive foci development have been detected and many are categorized as antioxidants. The validity of this system as a tool for rapid detection of carcinogenic and chemopreventive agents is discussed.