Higher activity of 8-oxo-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) coincides with lower background levels of 8-oxo-2′-deoxyguanosine in DNA of fetal compared with maternal mouse organs

Mammalian homologues of Escherichia coli MutT, a protein having 8-oxo-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity, are thought to play the same role in preventing the incorporation of promutagenic 8-oxo-2′-deoxyguanosine (8-oxo-dG) into DNA. One could thus expect that higher activity of 8-oxo-dGTPase should correlate with a lower background level of 8-oxo-dG in nuclear DNA. During transplacental carcinogenesis experiments, in control healthy Swiss mice on day 18 of gestation we found consistently lower levels of 8-oxo-dG in DNA in fetal livers and lungs (1.74 ± 0.04 SE and 1.49 ± 0.08 SE 8-oxo-dG/105 dG, respectively; pooled organs of fetuses of 8 dams) as compared with maternal organs (3.05 ± 0.20 SE and 3.08 ± 0.17 SE 8-oxo-dG/105 dG, respectively; n = 8). The 8-oxo-dGTPase activity determination in the same organs revealed that the lower levels of 8-oxo-dG in fetal DNA did, indeed, coincide with higher 8-oxo-dGTPase activity (48.8 ± 2.6 SE and 52.5 ± 2.5 SE U/mg protein in livers and lungs, respectively); and vice versa, higher 8-oxo-dG levels in DNA of maternal organs were associated with lower levels of 8-oxo-dGTPase activity (24.3 ± 1.3 SE and 4.7 ± 0.6 SE U/mg protein, as above). Without excluding other reasons for the relatively low 8-oxo-dG background in DNA of fetal tissues (e.g., higher level of antioxidants and antioxidative enzymes; more efficient DNA repair), this inverse relationship may support or at least does not contradict the concept of a guardian role of 8-oxo-dGTPase against 8-oxo-dGTP mutagenicity in mammalian cells.