The ability of liver extracts from different-aged rats to repair 'mis-instructive' and 'non-instructive' lesions of DNA.
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.
Pardini
C
C
Istituto di Mutagenesi e Differenziamento CNR, Pisa, Italy.
Mariani
L
L
Voliani
M
M
Rainaldi
G
G
Citti
L
L
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000502:physiology*; D008110:Liver Extracts; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats; D011916:Rats, Inbred F344
D008110:Liver Extracts; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D004706:Endodeoxyribonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase