Effect of regeneration and hyperplasia on levels of DNA base oxidation in rat liver.
Elevations of oxidatively modified DNA bases have been associated with a variety of carcinogens and tumor promoters, and implicated in causation of cancer. Since carcinogen exposure can induce cell proliferation, the relationship between induction of cell proliferation and levels of DNA base oxidation was examined. Cell proliferation was induced in livers of male F344 rats by stimuli of either regeneration or hyperplasia. Levels of DNA base oxidation were evaluated by measuring 8-OH-deoxyguanosine/deoxyguanosine (8-OHdG/dG) ratios by HPLC in enzymatic digests of DNA isolates. Despite induction of cell proliferation, hepatic levels of 8-OHdG/dG were not increased at 1, 2, 3 or 5 days after any of these treatments. Results of the present work suggest that the mechanism of elevated levels of DNA base oxidation is not directly related to induction of cell proliferation.
Murkofsky
R L
RL
Chemical Industry Institute of Toxicology, Research Triangle, Park, NC 27709.
Glover
S E
SE
Miller
R T
RT
Popp
J A
JA
Cattley
R C
RC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D002455:Cell Division; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D010084:Oxidation-Reduction; D010634:Phenobarbital; D011743:Pyrimidines; D051381:Rats; D011916:Rats, Inbred F344
D011743:Pyrimidines; C006253:pirinixic acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002251:Carbon Tetrachloride; D003849:Deoxyguanosine; D010634:Phenobarbital