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/10(5) 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/10(5) 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.
Bialkowski
K
K
Laboratory of Comparative Carcinogenesis, National Cancer Institute, SAIC Frederick, MD 21702-1201, USA. karolb@mail.ncifcrf.gov
Bialkowska
A
A
Anderson
L M
LM
Kasprzak
K S
KS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000378:metabolism; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine