EVIDENCE FOR IN-VIVO NON-MUTAGENICITY OF THE CARCINOGEN HYDRAZINE SULFATE IN TARGET TISSUES OF LACZ TRANSGENIC MICE

Transgenic mouse models permit the confirmation of in vitro mutagenici ty in vivo without the constraints in the selection of tissues imposed by other in vivo assays, This feature is of particular importance in the determination of mutagenicity in the target tissues of carcinogens , especially those that are in vitro mutagens, Such information is cri tical in the determination of whether a chemical is carcinogenic via a genotoxic or non-genotoxic mechanism, Hydrazine sulfate is an in vitr o mutagen that induces lung and liver tumours in mice, Transgenic mice from strain 40.6 (Muta(TM)mouse) were administered single oral doses up to a toxic concentration (400 mg/kg). No dose induced any lacZ muta tions in lung, liver or bone marrow, Since the highest single dose use d is higher than the cumulative dose that induced tumours in previous studies, it may be that either hydrazine sulfate is genotoxic in targe t tissues in vivo only when given in multiple doses or that it is a no ngenotoxic carcinogen.