Mammalian MTH1
proteins, homologs of Escherichia coli MutT, are
enzymes decomposing
8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) to
8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-monophosphate and inorganic
pyrophosphate. They play an antimutagenic role by preventing the incorporation of promutagenic
8-oxo-dGTP into
DNA. MTH1 gene expression is higher in some physiological types of mammalian cells and in numerous
cancer cells, but the mechanism of that upregulation still remains unclear. It has been hypothesized that MTH1 expression might be associated with a proliferation rate of the cells. Therefore, we tested this hypothesis by comparing the functional levels of MTH1 gene expression measured as the
8-oxo-dGTPase activity of its
protein products in normal mouse livers and hepatectomized regenerating livers. Although the proliferation rate of the hepatocytes in the regenerating livers was much higher than that in control livers, as confirmed by immunohistochemical assay of
proliferating cell nuclear antigen, the
8-oxo-dGTPase activity was not different. In a second approach, we used 57 lines of human
cancer cells in which
8-oxo-dGTPase activity was measured and confronted with cell population doubling time. No significant correlations between
8-oxo-dGTPase activity and proliferation rate were observed within groups of six
leukemia, eight
melanoma, nine lung, seven colon, six central nervous system, six ovarian, eight renal, and seven
breast cancer cell lines. Thus, we conclude that the MTH1 expression manifested as the
8-oxo-dGTPase activity of its
protein products in mammalian cells is not associated with proliferation rate. Our results will help in further testing of the hypothesis that MTH1 overexpression may be a specific marker of
carcinogenesis and/or oxidative stress.