OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2'-deoxyguanosine levels are unchanged.
This study was set up to investigate the relationships between the formation and removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day 16 of gestation) as compared to adult rats. The hypothesis addressed was whether the rapidly dividing foetal tissue has an enhanced requirement of DNA repair providing protection against potentially mutagenic DNA damages such as 8-oxodG. The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We found a 2-3-fold increased incision activity in the foetal control tissue, together with a 3-15-fold increase in mRNA of OGG1 as compared to liver tissue from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as compared to the adult groups. To increase the levels of 8-oxodG, the rats received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound induced significant levels of 8-oxodG in male rat livers 5h after the injection and in the foetuses 24h after the injection, while the female rats showed no increase in 8-oxodG. The incision activity was slightly depressed in both male and female liver tissue and in the foetal tissue 5h after the injection, but significantly increased from 5 to 24h after the injection. However, it did not reach levels significantly above the control levels. In conclusion, this study confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract.
Riis
Bente
B
Department of Clinical Pharmacology Q7642, Copenhagen University Hospital, Denmark.
Risom
Lotte
L
Loft
Steffen
S
Poulsen
Henrik Enghusen
HE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000831:Animals, Newborn; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000235:genetics* / Q000378:metabolism; D009595:Nitroparaffins / Q000633:toxicity; D016133:Polymerase Chain Reaction; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents
D017931:DNA Primers; D009595:Nitroparaffins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D012997:Solvents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine; C016617:2-nitropropane; D011407:Propane