Interindividual variation in the activity of O6-methyl guanine-DNA methyltransferase and uracil-DNA glycosylase in human organs

Carcinogenesis. 1983 Dec;4(12):1565-8. doi: 10.1093/carcin/4.12.1565.

Abstract

As a step towards understanding the significance of DNA repair enzymes in the protection against genotoxic and carcinogenic agents, we have examined the activity of O6-methyl-guanine-DNA methyltransferase and uracil-DNA glycosylase in adult human liver, stomach, small intestine and colon. Liver had on average a 5- to 8-fold higher activity of O6-MeG-DNA methyltransferase than the other organs and showed about an 8-fold inter-individual variation. In colon and small intestine an even larger inter-individual variation was observed (10- and 40-fold, respectively). In two colon tumors examined the activity of O6-MeG-DNA methyltransferase was several fold higher than in non-neoplastic colon mucosa from the same individuals, while uracil-DNA glycosylase activity was essentially equal in neoplastic and non-neoplastic tissues. O6-MeG-DNA methyltransferase activities in two gastric tumors examined were not higher than in average non-neoplastic tissue. In general the activity of uracil-DNA glycosylase did not correlate with the O6-MeG-DNA methyltransferase activity. The inter-individual variation of this enzyme in the activity was only 3-fold in liver and normal stomach, but varied 5.5 and 60-fold in colon and small intestine, respectively. In conclusion, we have found that O6-MeG-DNA methyltransferase as well as uracil-DNA glycosylase activity vary considerably between different tissues as well as between different individuals. Whether this variation has a genetic basis or reflects variation in 'life style' is not known.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Colon / enzymology*
  • Colonic Neoplasms / enzymology
  • DNA Glycosylases*
  • Female
  • Humans
  • Intestine, Small / enzymology*
  • Kinetics
  • Liver / enzymology*
  • Male
  • Methyltransferases / metabolism*
  • Middle Aged
  • N-Glycosyl Hydrolases / metabolism*
  • O(6)-Methylguanine-DNA Methyltransferase
  • Stomach / enzymology*
  • Stomach Neoplasms / enzymology
  • Tissue Distribution
  • Uracil-DNA Glycosidase

Substances

  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase