The transgenic Tg.AC mouse model for identification of chemical carcinogens

The Tg.AC (zetaglobin promoted v-Ha-ras) transgenic mouse is being evaluate d as a short-term carcinogenicity bioassay. In order to harmonize the evalu ation effort in diverse laboratories, an operational bioassay protocol has been established. Data, based principally on retrospective assay of known c arcinogens or tumor promoters and non-carcinogens, are presented that suppo rt the operational protocol. The Laboratory of Environmental Carcinogenesis and Mutagenesis at the NIEHS has been evaluating transgenic rodent models for utility in differentiating carcinogens from non-carcinogens. Our main a pproach in this method development effort has been to retrospectively study responses of the models to chemicals of known rodent carcinogenic potentia l. To this end we have tested mainly chemicals that have been previously st udied in chronic rat and/or mouse bioassays by the National Toxicology Prog ram. Development of the data base and assessment of the utility of the mode ls will be immeasurably aided by the availability of a standardized experim ental protocol. The purpose of this communication is to present the element s of the Laboratory of Environmental Carcinogenesis and Mutagenesis Tg.AC m ouse bioassay protocol and to show experimental results that led to the dev elopment of our study design. (C) 1998 Elsevier Science Ireland Ltd. All ri ghts reserved.