Medium-term Rat Liver Bioassay for Rapid Detection of Hepatocarcinogenic Substances.

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Abstract
We have developed a medium-term liver bioassay system for rapid detection of carcinogenic agents using male F344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system is fundamen-tally based on the two-stage hypothesis with regard to tumor production, employing initiation by diethylnitrosamine (200mg/kg, ip) in the first stage and test chemical administration during the second, in combination with 2/3 partial hepatectomy. It requires only 8 weeks for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically-demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 277 chemicals/substances have already been analyzed in our laboratory and the efficacy of the system for hepatocarcinogens has thereby been well established. This bioassay is increasingly becoming regarded as an appropriate alternative test system for carcinogenicity risk assessment. It is particularly useful for studies which require many experimental groups and for evaluation of chemopreventive agents.

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