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通过胃肠外和胃内注射1,2 - 二甲基肼,在喂食胰蛋白酶和他莫昔芬饮食的大鼠中诱导结肠腺癌。

Induction of colon adenocarcinomas in rats fed trypsin and tamoxifen diets by parenteral and intragastric 1,2-dimethylhydrazine.

作者信息

Gershbein L L

机构信息

Northwest Institute for Medical Research, John F. Kennedy Health Care Corporation, Chicago, IL 60634.

出版信息

Res Commun Mol Pathol Pharmacol. 1994 Sep;85(3):347-50.

PMID:7827809
Abstract

Male Sprague-Dawley rats, 25 days of age, were placed on a control ration and diets containing trypsin (2429 u/g) and tamoxifen (initial level: 4 PPM) at which time, 1,2-dimethylhydrazine was injected s.c. at 20 mg base/kg and continued once/week for 20 weeks. Most of the animals were killed 65 days after injection 20. In view of weight losses, the tamoxifen supplement was decreased to a final level of 0.50 PPM without intervening control diet feeding. The total number of colon adenocarcinomas and the distribution in the proximal and distal portions did not differ significantly from the respective controls and the tumor frequencies in the small intestine were not remarkable. However, the general animal conditions, weight changes and the presence of other tumor types were more extreme as compared to a similar trypsin supplement reported for rats administered carcinogen by gavage once weekly for 15 consecutive weeks. With the latter series, colon adenocarcinoma frequencies were markedly decreased.

摘要

25日龄的雄性斯普拉格-道利大鼠被给予对照日粮以及含有胰蛋白酶(2429单位/克)和他莫昔芬(初始水平:4 ppm)的日粮,此时,以20毫克碱基/千克的剂量皮下注射1,2-二甲基肼,并持续每周一次,共20周。大多数动物在第20次注射后65天被处死。鉴于体重减轻,他莫昔芬补充剂的最终水平降至0.50 ppm,期间未给予对照日粮。结肠腺癌的总数以及在近端和远端部分的分布与各自的对照组相比无显著差异,小肠中的肿瘤发生率也不显著。然而,与报道的连续15周每周一次经口灌胃给予致癌物的大鼠类似胰蛋白酶补充剂相比,一般动物状况、体重变化和其他肿瘤类型的出现更为严重。在后一组实验中,结肠腺癌的发生率显著降低。

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