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.