MUTAGENICITY OF THE POTENT RAT HEPATOCARCINOGEN 6BT TO THE LIVER OF TRANSGENIC (LACI) RATS - CONSIDERATION OF A REDUCED MUTATION ASSAY PROTOCOL

6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after o nly 2-3 months of dietary administration in a riboflavin-deficient die t. This azocarcinogen has been evaluated in a Big Blue(TM) F344 transg enic rat (lacI) gene mutation assay, In a reproduction of the early st ages of the carcinogenesis bioassay of this agent, rats were maintaine d on a riboflavin-deficient diet and were given 10 consecutive daily d oses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose, The livers of 6BT-treat ed rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figu res, An similar to 10-fold increase in the mutation frequency of DNA i solated from an aliquot of the combined liver homogenates of 6BT-treat ed rats was observed over that obtained from an equivalent aliquot fro m control animals, Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue(TM ) rat livers, These data extend the sensitivity of this transgenic ass ay to include azo hepatocarcinogens. The determination of mutation fre quencies using pooled tissue samples represented a major resource-savi ng adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.