Expression of O6-methylguanine--DNA methyltransferase and uracil--DNA glycosylase in human placentae from smokers and non-smokers.
DNA repair capacity is likely to be a critical factor in mutagenesis and carcinogenesis, as well as for the response to some cytostatics. We have studied inter- and intra-individual variation in the activities of O6-methylguanine--DNA methyltransferase (O6-MT) and uracil--DNA glycosylase (UDG) in 35 placentae from smokers and non-smokers. The maximum interindividual variation in the activities of O6-MT and UDG were 8.3- and 7.7-fold, respectively. The corresponding intraindividual variations were 2.7- and 3.3-fold. Generally, a high level of O6-MT activity was accompanied by a high O6-MT mRNA level, but no such correlation was seen for UDG. These results were not due to degradation of the enzymes or mRNAs after delivery. No correlation between the activities of O6-MT and UDG was observed, indicating that they are differentially regulated. A 1.4-fold (P < or = 0.05) higher activity of O6-MT was observed in smokers as compared to non-smokers, indicating a small, but statistically significant difference. No significant difference was observed for UDG. Our results demonstrate that DNA repair capacities vary largely between different individuals, and that environmental factors may modulate the expression of DNA repair enzymes.
Slupphaug
G
G
UNIGEN Center for Molecular Biology, University of Trondheim, Norway.
Lettrem
I
I
Myrnes
B
B
Krokan
H E
HE
D045647:DNA Glycosylases; D004260:DNA Repair / Q000502:physiology; D004790:Enzyme Induction; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D008780:Methyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010920:Placenta / Q000201:enzymology* / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase
D012333:RNA, Messenger; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase