Increased susceptibility to oxidative DNA damage in regenerating liver.
Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)-induced levels of 8-hydroxy-2'-deoxyguanosine (oh8dG) in the nuclear DNA of regenerating liver [24, 48, 72 h and 7 days after partial hepatectomy (PH)] of male Sprague-Dawley rats were analysed for the verification of a hypothesis that the high susceptibility of proliferating hepatocytes to DNA damage is related to the well-known high susceptibility to carcinogens after PH. Interestingly, the spontaneous level of nuclear oh8dG in regenerating liver was significantly decreased (P < 0.01) at 48 h after PH (1.05 +/- 0.31 oh8dG/10(5)dG) compared with the level in normal rats (1.90 +/- 0.41). 2-NP induced an oh8dG level of 4.49 +/- 0.86 in nuclear DNA of rat liver without PH. However, in rats administered 2-NP (injections were performed 6 h before each sacrifice) after PH, the oh8dG level was significantly higher at 24 h (5.45 +/- 1.41, P < 0.05), 48 h (5.85 +/- 0.88, P < 0.01) and 72 h (5.67 +/- 1.07, P < 0.05) after PH than those with 2-NP exposure alone. Therefore, it is suggested that nuclear DNA in proliferating hepatocytes is in a stage susceptible to exogenous attack by 2-NP, and consequently this phenomenon might be related to the induction of hepatocarcinogenesis after PH.
Adachi
S
S
Department of Public Health, Saitama Medical School, Japan.
Kawamura
K
K
Takemoto
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004198:Disease Susceptibility; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D009595:Nitroparaffins; D010084:Oxidation-Reduction; D011407:Propane / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009595:Nitroparaffins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; C016617:2-nitropropane; D011407:Propane