Bioactivation of dimethylnitrosamine in intrasanguinous host-mediated assay and its association with in vitro mutagenesis assays.
These studies have revealed the usefulness of in vivo intrasanguine host-mediated assay (HMA) to detect point mutations. Mutations were found to occur at a significant rate in Salmonella typhimurium G-46 employed as indicator organisms recovered from liver, lung, kidney and spleen of DMN-treated animals compared to negative control animals. These differences were true for both male and female animals. The number of Salmonella typhimurium G-46 recovered from the testes was not large enough to make a valid judgment about mutations occurring in testes. The results from in vitro studies do not match with the in vivo host-mediated assay results for mutants occurring in spleen from the male and the female mice. The results also do not correlate for in vitro and in vivo studies involving female kidneys. These results suggest there may be no one-to-one correlation between the organ bioactivation in vitro and in vivo, and predictions of in vivo target organ cannot always be made from in vitro studies with isolated microsomal enzymes.
D000818:Animals; D004128:Dimethylnitrosamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods*; D009928:Organ Specificity; D012486:Salmonella typhimurium / Q000235:genetics; D012737:Sex Factors; D013154:Spleen / Q000378:metabolism
D004128:Dimethylnitrosamine