Adachi S, Kawamura K, Takemoto K
Department of Public Health, Saitama Medical School, Japan.
Carcinogenesis. 1994 Mar;15(3):539-43. doi: 10.1093/carcin/15.3.539.
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.
分析了雄性Sprague-Dawley大鼠再生肝（部分肝切除术后[PH]24、48、72小时和7天）细胞核DNA中8-羟基-2'-脱氧鸟苷（oh8dG）的自发水平和由肝癌致癌物（2-硝基丙烷，2-NP）诱导的水平，以验证增殖肝细胞对DNA损伤的高易感性与PH后对致癌物的众所周知的高易感性相关这一假设。有趣的是，与正常大鼠（1.90±0.41）相比，再生肝中oh8dG的自发水平在PH后48小时（1.05±0.31 oh8dG/10(5)dG）显著降低（P<0.01）。2-NP在未进行PH的大鼠肝细胞核DNA中诱导的oh8dG水平为4.49±0.86。然而，在PH后给予2-NP的大鼠（每次处死前6小时注射）中，PH后24小时（5.45±1.41，P<0.05）、48小时（5.85±0.88，P<0.01）和72小时（5.6
