INCREASED SUSCEPTIBILITY TO OXIDATIVE DNA-DAMAGE IN REGENERATING LIVER

Spontaneous and hepatocarcinogen (2-nitropropane, 2-NP)induced levels of 8-hydroxy-2'-deoxyguanosine (oh(8)dG) 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 oh(8)dG in regenerating liver was significantly decreased (P < 0.01) at 48 h after PH (1.05 +/- 0.31 oh(8)dG/10(5)dG) compared with the level in normal rats (1.90 +/- 0.41). 2-NP induced an oh(8)dG 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 oh(8)dG 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.