Increased rOGG1 expression in regenerating rat liver tissue without a corresponding increase in incision activity.
Rapidly proliferating tissue with synthesis of a large number of cellular macromolecules including DNA, may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. This hypothesis was addressed by assessing the incision activity and the mRNA level of the DNA repair protein rat 8-oxodeoxyguanosine glycosylase (rOGG1) as well as the level of the oxidative stress biomarker 8-oxodeoxyguanosine (8-oxodG) in rat liver tissue before and after partial hepatectomy. A five-fold increase in rOGG1 expression was found at 24h after PHx relative to the control levels. At 48h the rOGG1 mRNA levels were reduced to three-times the control values. The corresponding incision activities of rOGG1 in the crude tissue extract as measured by the incision assay were slightly increased both at 24 and 48h after partial hepatectomy although the changes failed to be statistically significant (P=0.07 and 0.06, respectively). The levels of 8-oxodG were unaltered at 24h but increased to 1.8 times the control values at 48h after partial hepatectomy. The study showed that rapid proliferating liver tissue in vivo had an increased expression of the DNA repair protein rOGG1, without significantly increased incision activity on a 8-oxodG-containing substrate and with unchanged levels of 8-oxodG/10(6) dGuo after 24h of regeneration. At 48h the rOGG1 expression was decreased, and the levels of 8-oxodG/10(6) dGuo increased but still significant changes in the incision activity could not be detected. Thus, we can conclude that the rOGG1 expression is temporarily up-regulated by the proliferating events elicited by partial hepatectomy.
Riis
Bente
B
Department of Clinical Pharmacology Q7642, Copenhagen University Hospital, Dk-2100, Copenhagen, Denmark.
Risom
Lotte
L
Loft
Steffen
S
Poulsen
H E
HE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004790:Enzyme Induction; D006498:Hepatectomy; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D012313:RNA; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D017931:DNA Primers; D012333:RNA, Messenger; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine