Evaluation of three metabolic activation systems by a forward mutation assay in Salmonella

The strain SV3 of Salmonella typhimurium was used as the indicator bacterium in the intrasanguineous host-mediated mutagenicity assay. Bacterial distribution and spontaneous mutation frequency were determined after intravenous injection of SV3 into CD1 male mice. Bacteria were cleared at an exponential rate from the blood stream and recovered mainly from the liver and in smaller quantities from the lungs and kidneys. No bactericidal effect was observed during incubation within the animal, and bacterial division occurred in the liver and probably in the kidneys. The significance of an increased mutation frequency of bacteria recovered from untreated animals is discussed. Mutation induction was measured in bacteria recovered from liver, lungs and kidneys of CD1 mice and CD rats treated with dimethylnitrosamine (DMN). The sensitivity of the intrasanguineous host-mediated technique was compared with the sensitivity of the assay in vitro with microsomal preparations from each tissue and host. Activation by isolated perfused liver and lungs from CD rats was included for comparison with the results from experiments in vivo and in vitro.