TISSUE-SPECIFIC INDUCTION OF MUTATIONS BY STREPTOZOTOCIN IN-VIVO

Streptozotocin has been reported to induce DNA damage in mouse liver a lthough malignant tumors were not induced in this organ. DNA damage ha d not yet been monitored in the mouse kidney which was the tumor targe t organ in two mouse studies. In order to elucidate target organ speci ficity of genotoxicity and of tumorigenesis, we investigated the induc tion of DNA damage (microgel electrophoresis assay) and mutations (Lad transgenic mouse mutation assay) in the fiver and kidney of male C57B L/6 mice. Our results show that the microgel electrophoresis assay was more sensitive and revealed the genotoxic potential of streptozotocin at lower doses than the mutation assay. It was, however, less specifi c in that DNA damage was induced both in target and non-target tissues of carcinogenesis at a similar potency. In contrast, the mutation ana lysis revealed the kidney to be more sensitive when the induced mutati on frequencies are expressed as a multiple of the respective spontaneo us rates. We conclude, therefore, that the carcinogenic organotropy of streptozotocin correlates better with its tissue-specific mutagenicit y than with its pattern of inducing DNA damage when the two in vivo ge notoxicity assays mentioned above are used. A combined use of the micr ogel electrophoresis assay and the transgenic mouse mutation assay is proposed for investigations of tissue-specific genotoxicity.