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氨基甲酸乙烯酯诱导A系小鼠肺肿瘤的化学预防

Chemoprevention of vinyl carbamate-induced lung tumors in strain A mice.

作者信息

Gunning W T, Kramer P M, Lubet R A, Steele V E, Pereira M A

机构信息

Department of Pathology, Block Health Science Building, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614-5806, USA.

出版信息

Exp Lung Res. 2000 Dec;26(8):757-72. doi: 10.1080/01902140150216800.

Abstract

The ability of potential chemopreventive agents to prevent vinyl carbamate-induced lung tumors was determined in 2 different experiments. Female strain A mice administered intraperitoneally either a single injection of 60 mg/kg vinyl carbamate that induced 24.0 +/- 1.72 tumors/mouse at 24 weeks or 2 injections of 16 mg/kg vinyl carbamate each (32 mg/kg total dose) that induced 43.2 +/- 3.2 tumors/mouse at 20 weeks. Lung carcinomas were found as early as 16 weeks. Dexamethasone and piroxicam provided in the diet were found to significantly inhibit lung tumors induced by 60 mg/kg vinyl carbamate at 24 weeks whereas myo-inositol also provided in the diet, did not significantly inhibit tumor formation. In animals given 6 16-mg/kg doses of vinyl carbamate, tumor multiplicity was reduced roughly 25% by alpha-difluoromethylornithine and green tea and reduced 50% by dexamethasone and piroxicam. Combinations of these agents were also tested using a total dose of 32 mg/kg of vinyl carbamate. Although alpha-difluoromethylornithine and green tea did not result in a significant inhibition of lung tumor formation if used alone, the combination of alpha-difluoromethylornithine and green tea resulted in a significant reduction of tumor multiplicity. The combinations of alpha-difluoromethylornithine or green tea with either dexamethasone or piroxicam or the combination of dexamethasone and piroxicam did not decrease tumor multiplicity greater than achieved by dexamethasone and piroxicam alone. In summary, selected chemopreventive agents previously shown to inhibit lung tumors by other chemical carcinogens also inhibited vinyl carbamate-induced lung tumors.

摘要

在两项不同的实验中测定了潜在化学预防剂预防氨基甲酸乙烯酯诱发肺肿瘤的能力。给雌性A系小鼠腹腔内注射一次60mg/kg的氨基甲酸乙烯酯,在24周时每只小鼠诱发24.0±1.72个肿瘤;或者注射两次16mg/kg的氨基甲酸乙烯酯(总剂量32mg/kg),在20周时每只小鼠诱发43.2±3.2个肿瘤。早在16周时就发现了肺癌。发现饮食中添加的地塞米松和吡罗昔康可显著抑制24周时60mg/kg氨基甲酸乙烯酯诱发的肺肿瘤,而饮食中添加的肌醇则不能显著抑制肿瘤形成。在给予6次16mg/kg剂量氨基甲酸乙烯酯的动物中,α-二氟甲基鸟氨酸和绿茶使肿瘤多发性降低约25%,地塞米松和吡罗昔康使肿瘤多发性降低50%。还使用32mg/kg总剂量的氨基甲酸乙烯酯对这些药剂的组合进行了测试。虽然单独使用α-二氟甲基鸟氨酸和绿茶不会显著抑制肺肿瘤形成,但α-二氟甲基鸟氨酸和绿茶的组合可显著降低肿瘤多发性。α-二氟甲基鸟氨酸或绿茶与地塞米松或吡罗昔康的组合,或地塞米松和吡罗昔康的组合,均未使肿瘤多发性降低超过单独使用地塞米松和吡罗昔康所达到的程度。总之,先前显示能抑制其他化学致癌物诱发肺肿瘤的某些化学预防剂,也能抑制氨基甲酸乙烯酯诱发的肺肿瘤。

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