Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate, a mutagenic substrate for DNA synthesis, in human cells

Biochemistry. 1995 Jan 10;34(1):89-95. doi: 10.1021/bi00001a011.


8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a potent mutagenic substrate for DNA synthesis. The present study deals with generation and degradation of 8-oxo-dGTP in the nucleotide pool of human cells. (1) 8-Oxo-dGTP can be generated not only by direct oxidation of dGTP but also by phosphorylation of 8-oxo-dGDP by nucleoside diphosphate kinase. (2) 8-Oxo-dGTP is rapidly degraded to 8-oxo-dGMP by cellular 8-oxo-dGTPase activity. 8-Oxo-dGMP thus produced cannot be rephosphorylated; guanylate kinase, which phosphorylates both GMP and dGMP to the corresponding nucleoside diphosphates, is totally inactive for 8-oxo-dGMP. (3) 8-Oxo-dGMP is further degraded to 8-oxo-deoxyguanosine by a nucleotidase. The enzyme was partially purified from an extract of human Jurkat cells, and the mode of action was elucidated. 8-Oxo-dGMP is the most preferred substrate of the enzyme, and other nucleoside monophosphates are cleaved at significantly lower rates: Km for 8-oxo-dGMP is 10 times lower than that for dGMP, the second best substrate for the enzyme. The enzyme appears to convert 8-oxo-dGMP, which accumulates in the cellular nucleotide pool, to a form readily excretable to the cell exterior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell-Free System
  • DNA / biosynthesis*
  • Deoxyguanine Nucleotides / biosynthesis
  • Deoxyguanine Nucleotides / metabolism*
  • Guanylate Kinases
  • Humans
  • Mutagens / metabolism*
  • Nucleoside-Diphosphate Kinase / metabolism
  • Nucleoside-Phosphate Kinase / metabolism
  • Nucleotidases / metabolism
  • Phosphorylation
  • Substrate Specificity
  • Tumor Cells, Cultured


  • Deoxyguanine Nucleotides
  • Mutagens
  • 8-oxodeoxyguanosine triphosphate
  • DNA
  • Nucleoside-Phosphate Kinase
  • Nucleoside-Diphosphate Kinase
  • Guanylate Kinases
  • 8-oxo-dGMPase
  • Nucleotidases