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.