用于非遗传毒性（Ames试验阴性）肝癌致癌性短期预测的大鼠肝脏体内复制性DNA合成试验：日本非遗传毒性致癌物研究组的一项协作研究
Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.
作者信息
Uno Y, Matsuura K, Miyagawa M, Takasawa H, Tanifuji H, Abe K, Akimoto A, Asanoma K, Baba K, Daigo H, Hagiwara T, Hirano K, Inoue T, Kawano Y, Kijima K, Sato F, Shibata-Yoshida K, Yamamura E
机构信息
Toxicology Laboratory, Yokohama Research Center, Mitsubishi Chemical Co., Japan.
出版信息
Toxicol Lett. 1999 Sep 20;109(1-2):105-14. doi: 10.1016/s0378-4274(99)00129-0.
A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.
开展了一项合作研究，以评估使用大鼠肝脏进行的复制性DNA合成（RDS）试验，能否在长期生物测定有效的剂量水平下，通过每日给药三次或七次来检测非遗传毒性（艾姆斯试验阴性）的肝癌致癌物。该检测方法得到了14名参与者的充分验证。在测试的六种化合物中，四氯化碳（50和100mg/kg）、氯贝丁酯（125和250mg/kg）、己烯雌酚（0.125和0.25mg/kg）和氨基甲酸乙酯（100mg/kg）给出了阳性结果，氨基甲酸甲酯（200和400mg/kg）产生了不确定的影响，而DL-乙硫氨酸（125mg/kg）未能提高RDS。这些发现表明，RDS试验可以在长期生物测定所使用的剂量水平下，通过短期给药检测出许多非遗传毒性的大鼠肝癌致癌物。
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