[Intensity of liver tumor promotion effects in rats given repeated oral administrations of benzimidazole compounds].

H Onodera, K Mitsumori, C Uneyama, K Yasuhara, K Takegawa, M Takahashi
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Abstract

Liver tumor-promoting effects of anthelminthic agents, febantel (Feb), fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage carcinogenesis model. Five-week-old male F344 rats were initiated with or without diethylnitrosamine (DEN) and one week later given diet containing Fen (3600, 1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100 or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number or area of Cx32 positive spots per hepatocyte was significantly decreased in treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone group. GST-P positive foci was significantly increased in DEN + Fen groups treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that these three compounds have liver tumor promotion effects and the promoting action in Oxf is most strong among them.

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[反复口服苯并咪唑类化合物大鼠肝肿瘤促进作用的强度]。
在啮齿动物2期癌变模型中,研究了驱虫药非班特尔(Feb)、芬苯达唑(Fen)或奥芬达唑(Oxf)对肝脏肿瘤的促进作用。5周龄雄性F344大鼠首先给予或不给予二乙基亚硝胺(DEN),一周后给予含芬(3600、1800、600、200或70 ppm)、Feb(2000、1000、500或100 ppm)或Oxf(500、250、100或10 ppm)的日粮8周。DEN + Feb和DEN + Oxf处理组均可诱导CYP1A1/2,且以DEN + Oxf处理组诱导最明显。在这些处理组中,CYP2B1和CYP4AI也被诱导。与单独DEN组相比,除DEN + Oxf 100 ppm组外,各处理组每个肝细胞Cx32阳性斑点的数量或面积均显著减少。DEN + Fen组(1800ppm及以上)、DEN + Feb组(1000ppm及以上)和DEN + Oxf组(250ppm及以上)GST-P阳性灶显著增加。上述结果提示,这3种化合物均具有肝肿瘤促进作用,其中对Oxf的促进作用最强。
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