Yamamoto F, Kasai H, Togashi Y, Takeichi N, Hori T, Nishimura S
Biology Division, National Cancer Center Research Institute, Tokyo.
Jpn J Cancer Res. 1993 May;84(5):508-11. doi: 10.1111/j.1349-7006.1993.tb00168.x.
Long-Evans Cinnamon (LEC) rats, a mutant strain originating from Long-Evans rats, spontaneously develop hereditary hepatitis followed by hepatocellular carcinoma. The hepatic disorder in LEC rats is associated with their abnormal copper metabolism; metal-catalyzed reactions often give rise to oxygen radicals, which may be related to the carcinogenesis. By means of high-pressure liquid chromatography with electrochemical detection, cellular DNA damage caused by oxygen radicals can be assessed in terms of the amount of 8-hydroxydeoxyguanosine (oh8dG). We assayed the amount of oh8dG in DNA of liver, kidneys, and brain of LEC and Long-Evans Agouti (LEA) control rats in seven groups (n = 3 to 6) aged from 5 weeks to 24 months. Control rats, a healthy sibling line, were age-matched. The amount of oh8dG was correlated with the severity of the age-related clinical symptoms in LEC rats. The amount was higher in LEC rats than in the controls, especially in the liver at the acute stage of hepatitis. These findings suggest that oxygen radicals may be important in the carcinogenesis that occurs in LEC rats.
长-伊文斯肉桂色（LEC）大鼠是源自长-伊文斯大鼠的一种突变品系，会自发发展为遗传性肝炎，随后发展为肝细胞癌。LEC大鼠的肝脏疾病与其异常的铜代谢有关；金属催化反应常常会产生氧自由基，这可能与致癌作用有关。通过采用电化学检测的高压液相色谱法，可以根据8-羟基脱氧鸟苷（oh8dG）的量来评估由氧自由基引起的细胞DNA损伤。我们测定了7组（n = 3至6）年龄从5周龄到24月龄的LEC大鼠以及作为对照的长-伊文斯刺豚鼠（LEA）大鼠的肝脏、肾脏和大脑DNA中的oh8dG含量。对照大鼠是健康的同胞品系，与LEC大鼠年龄匹配。oh8dG的量与LEC大鼠与年龄相关的临床症状的严重程度相关。LEC大鼠体内的oh8dG含量高于对照组，尤其是在肝炎急性期的肝脏中。这些发现表明，氧自由基可能在LEC大鼠发生的致癌过程中起重要作用。
