Fukushima Nobuyoshi, Kuromatsu Ryoko, Akiba Jun, Ando Eiji, Takata Akio, Sumie Shuji, Nakano Masahito, Nakamura Toru, Kawahara Akihiko, Torimura Takuji, Nakashima Osamu, Okuda Koji, Yano Hirohisa, Kage Masayoshi, Kojiro Masamichi, Sata Michio
Division of Gastroenterology, Department of Medicine, and ; Department of Gastroenterology, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka 810-8563, Japan.
Exp Ther Med. 2010 Sep;1(5):809-816. doi: 10.3892/etm.2010.132. Epub 2010 Jul 21.
The mechanism responsible for the development of hepatocellular carcinoma (HCC) in the setting of oxidative stress has yet to be clearly defined. We studied the role of oxidative stress in hepatocarcinogenesis in subjects without underlying chronic viral hepatitis. The subjects were 24 patients negative for serum hepatitis B surface antigen and hepatitis C antibody tests, who underwent hepatic resection for HCC (Group N). Subjects were excluded if diagnosed with liver disease predisposing to HCC. Immunohistochemical staining for oxidative stress-related markers was performed on non-cancerous liver regions. Resected liver tissues adjacent to HCC from 24 patients with chronic hepatitis B (Group B) and 21 patients with chronic hepatitis C (Group C) were also examined. The percentage of 8-hydroxydeoxyguanosine-positive hepatocytes in Group N was significantly lower than that in Group B and that in the combined population of Groups B and C. The percentage of the area positive for 4-hydroxynonenal in Group N was significantly higher than that in Groups B or C. Meanwhile, the percentage of the area positive for manganese superoxide dismutase in Group N was not different from that in Groups B and C. In conclusion, the mechanism of hepatocarcinogenesis through oxidative stress for patients without known liver disease predisposing to HCC may differ from that for patients with chronic viral hepatitis.
氧化应激背景下肝细胞癌（HCC）发生发展的机制尚未明确界定。我们研究了氧化应激在无潜在慢性病毒性肝炎患者肝癌发生过程中的作用。研究对象为24例血清乙肝表面抗原和丙肝抗体检测均为阴性、因HCC接受肝切除手术的患者（N组）。若诊断为易患HCC的肝脏疾病则排除在外。对非癌肝组织区域进行氧化应激相关标志物的免疫组化染色。还检查了24例慢性乙型肝炎患者（B组）和21例慢性丙型肝炎患者（C组）切除的与HCC相邻的肝组织。N组中8 - 羟基脱氧鸟苷阳性肝细胞的百分比显著低于B组以及B组和C组合并人群中的百分比。N组中4 - 羟基壬烯醛阳性区域的百分比显著高于B组或C组。同时，N组中锰超氧化物歧化酶阳性区域的百分比与B组和C组无差异。总之，对于无已知易患HCC肝脏疾病的患者，通过氧化应激发生肝癌的机制可能与慢性病毒性肝炎患者不同。
