Tsuda H, Asamoto M, Kagawa M, Uwagawa S, Inoue K, Inui M, Ito N
First Department of Pathology, Nagoya City University Medical School, Japan.
Carcinogenesis. 1988 Jun;9(6):1103-5. doi: 10.1093/carcin/9.6.1103.
The effect of deoxycholic acid (DCA) treatment subsequent to initiation of F344 male rats with N-methyl-N-nitrosourea (MNU), a wide spectrum carcinogen inducing tumors in many organs, was investigated. Rats were initially given four doses of MNU (50 mg/kg) i.p. within a 2-week period combined with a two-thirds partial hepatectomy performed at day 7 and then placed on basal diet containing DCA at concentrations of 0.313, 0.125, 0.050 and 0.020% for 21 weeks prior to final sacrifice. All organs studied were carefully examined histologically and histochemically for development of neoplastic and pre-neoplastic lesions. DCA enhanced the induction of glutathione S-transferase positive (GST-P+) liver cell foci in a dose-related manner. Furthermore groups of rats given DCA without prior MNU administration also developed dose-dependent numbers of pre-neoplastic liver lesions. In addition, increased numbers of small intestine tumors were apparent in DCA-treated animals although the difference was not significant. Induction of tumors in the thyroids, Zymbal glands, skin and peripheral nerves was not affected. The results indicate that DCA is a strong promoter of hepatocarcinogenesis with possible complete carcinogenicity in the liver and promotion potential for tumor development in the small intestine.
研究了在给F344雄性大鼠注射N-甲基-N-亚硝基脲（MNU，一种能在许多器官诱导肿瘤的广谱致癌物）后给予脱氧胆酸（DCA）治疗的效果。大鼠最初在2周内腹腔注射四剂MNU（50 mg/kg），并在第7天进行三分之二的部分肝切除术，然后在最终处死前21周置于含0.313%、0.125%、0.050%和0.020%DCA的基础饮食中。对所有研究的器官进行了仔细的组织学和组织化学检查，以观察肿瘤性和肿瘤前病变的发展。DCA以剂量相关的方式增强了谷胱甘肽S-转移酶阳性（GST-P+）肝细胞灶的诱导。此外，未预先给予MNU而给予DCA的大鼠组也出现了剂量依赖性的肿瘤前肝脏病变。此外，DCA处理的动物中小肠肿瘤数量增加，尽管差异不显著。甲状腺、齐默尔氏腺、皮肤和周围神经的肿瘤诱导未受影响。结果表明，DCA是肝癌发生的强促进剂，在肝脏可能具有完全致癌性，对小肠肿瘤发展具有促进潜力。
