Medium-term bioassays for carcinogens.

Abstract

Medium-term bioassay systems in rats have been developed for rapid detection of carcinogenic agents and have been introduced for practical use. There are two major systems: N-nitrosodiethylamine and partial hepatectomy in liver and multiorgan models. The first model takes eight weeks; it consists of an initial intraperitoneal injection of N-nitrosodiethylamine, six weeks' administration of test chemical(s) beginning two weeks later, partial hepatectomy at week 3, and analysis of immunohistochemically identified glutathione S-transferase placental form-positive liver-cell foci. Using this model, the potency of carcinogenic agents can be predicted satisfactorily, at least for those of which the liver is a target organ. The multi-organ models include wide-spectrum organ initiation by N-methyl-N-nitrosourea or combined, short treatment with several carcinogens sequentially and subsequent administration of test chemical(s) for 12-20 weeks. Although these systems require a longer time, their accuracy as organotropism-independent testing systems has been validated by whole-body histological examination. These approaches promise precise, rapid detection of carcinogenic agents and should bridge the gap between established methods for screening in vitro and long-term carcinogenicity testing, with their inherent disadvantages. Other medium-term bioassay methods are discussed in addition to our two systems.