The ability of liver extracts from different-aged rats to repair 'mis-instructive' and 'non-instructive' lesions of DNA

Mutat Res. 1992 Jan;275(1):1-6. doi: 10.1016/0921-8734(92)90002-7.


The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Endodeoxyribonucleases / metabolism
  • Liver / enzymology
  • Liver / physiology*
  • Liver Extracts
  • Male
  • Methyltransferases / metabolism
  • O(6)-Methylguanine-DNA Methyltransferase
  • Rats
  • Rats, Inbred F344


  • Liver Extracts
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Endodeoxyribonucleases
  • Deoxyribonuclease IV (Phage T4-Induced)
  • DNA-(Apurinic or Apyrimidinic Site) Lyase