2-Hydroxyadenine, a mutagenic form of oxidative DNA damage, is not repaired by a glycosylase type mechanism in rat organs

Mutat Res. 1998 Aug 7;408(2):121-7. doi: 10.1016/s0921-8777(98)00025-1.

Abstract

Oxygen radicals are known to play a role in causing cellular DNA damage, which is involved in carcinogenesis. 8-Hydroxyguanine (8-OH-Gua) is a major form of oxidative DNA damage and is known as a useful marker of DNA oxidation. Recently, we found another type of oxidative DNA damage, 2-hydroxyadenine (2-OH-Ade), which has a mutation frequency comparable to that of 8-OH-Gua. We compared the repair activities for two types of oxidative DNA damage, 8-OH-Gua and 2-OH-Ade, in 7-week-old male Sprague-Dawley (SD) rat organs. The repair activities were measured by an endonuclease nicking assay using 22 mer [32P]-end-labeled double-stranded DNA substrates, which contained either 8-OH-Gua (opposite C) or 2-OH-Ade (opposite T or C). In all of the SD rat organs we studied, the nicking activity for 2-OH-Ade was not detected, while that for 8-OH-Gua was clearly detected with the same conditions. Moreover, the 2-OH-Ade nicking activity was not induced in Wistar rat kidney extracts prepared after ferric nitrilotriacetate (Fe-NTA) treatment, which is known to increase 8-OH-Gua repair activity. These results suggest that 2-OH-Ade might not be repaired by the glycosylase type mechanism in mammalian cells.

MeSH terms

  • Animals
  • DNA Damage
  • DNA Repair* / drug effects
  • Endonucleases / metabolism*
  • Ferric Compounds / pharmacology
  • Guanine / analogs & derivatives
  • Guanine / metabolism*
  • Kidney / enzymology
  • Liver / enzymology
  • Lung / enzymology
  • Male
  • Nitrilotriacetic Acid / analogs & derivatives
  • Nitrilotriacetic Acid / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar

Substances

  • Ferric Compounds
  • 8-hydroxyguanine
  • Guanine
  • isoguanine
  • Endonucleases
  • Nitrilotriacetic Acid
  • ferric nitrilotriacetate