Kojima S, Shimomura H, Matsumori S
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan.
Anticancer Res. 2000 May-Jun;20(3A):1583-8.
We examined the elevation of glutathione (GSH) level in mouse liver and HepG2 cells after low-dose gamma-ray irradiation and its inhibitory effect on acetaminophen (AAP)- and cumene hydroperoxide (CHP)-induced hepatotoxicity. The liver GSH level in male ddY mice increased 2 hours after irradiation with 50 cGy of gamma-rays, reached a maximum at around 4 hours and returned almost to the control level by 12 hours. The effect of irradiation at 2 hours before AAP-treatment on the hepatotoxicity was then investigated in terms of glutamic pyruvic transaminase (GPT) activity in serum and lipid peroxide (malondialdehyde, MDA) content in the liver. GPT activity and MDA level were markedly increased at 24 hours post-treatment with AAP. Both increases were significantly suppressed by a single low-dose pre-irradiation with gamma-rays (50 cGy). The cellular GSH level of HepG2 cells increased about 3 hours after exposure to gamma-rays (50 cGy), peaked at 12 hours and returned almost to the time 0 value by 48 hours post-irradiation. Exposure of HepG2 cells to CHP induced time- and dose-dependent cytotoxicity, as judged from lactate dehydrogenase activity (LDH) released into the medium. Pre-irradiation with gamma-rays (50 cGy) at 6 hours before addition of 1 mM CHP to the cells significantly suppressed the elevation of LDH activity at 24 hours post-treatment. In both cases, the lowered GSH levels induced by AAP and CPH appeared to be restored to the control level by pre-irradiation with a low dose of gamma-rays. These results suggest that low-dose gamma-ray irradiation might be effective for the prevention of hepatotoxicity involving GSH deficiency.
我们研究了低剂量γ射线照射后小鼠肝脏和HepG2细胞中谷胱甘肽（GSH）水平的升高及其对乙酰氨基酚（AAP）和氢过氧化异丙苯（CHP）诱导的肝毒性的抑制作用。雄性ddY小鼠经50 cGyγ射线照射后2小时，肝脏GSH水平升高，约4小时达到峰值，12小时时几乎恢复到对照水平。然后，根据血清谷丙转氨酶（GPT）活性和肝脏脂质过氧化物（丙二醛，MDA）含量，研究AAP处理前2小时照射对肝毒性的影响。AAP处理后24小时，GPT活性和MDA水平显著升高。单次低剂量γ射线预照射（50 cGy）可显著抑制这两种升高。HepG2细胞暴露于γ射线（50 cGy）后约3小时，细胞内GSH水平升高，12小时达到峰值，照射后48小时几乎恢复到0时的值。从释放到培养基中的乳酸脱氢酶活性（LDH）判断，HepG2细胞暴露于CHP会诱导时间和剂量依赖性细胞毒性。在向细胞中添加1 mM CHP前6小时用γ射线（50 cGy）预照射，可显著抑制处理后24小时LDH活性的升高。在这两种情况下，AAP和CPH诱导的降低的GSH水平似乎通过低剂量γ射线预照射恢复到对照水平。这些结果表明，低剂量γ射线照射可能对预防涉及GSH缺乏的肝毒性有效。
