Interindividual variation in the activity of O6-methyl guanine-DNA methyltransferase and uracil-DNA glycosylase in human organs.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D003106:Colon / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology; D045647:DNA Glycosylases; D005260:Female; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013270:Stomach / Q000201:enzymology*; D013274:Stomach Neoplasms / Q000201:enzymology; D014018:Tissue Distribution; D051981:Uracil-DNA Glycosidase
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase