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注射1,2-二甲基肼的大鼠的氮摄入量与肿瘤发生

Nitrogen intake and tumorigenesis in rats injected with 1,2-dimethylhydrazine.

出版信息

J Nutr. 1976 Nov;106(11):1583-90. doi: 10.1093/jn/106.11.1583.

Abstract

Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic casein-sucorse deits containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numberous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol reose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Altough the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks.

摘要

对断奶时被分配到含7.5%、15%或22.5%蛋白质且含或不含2.5%尿素的等能量酪蛋白 - 蔗糖饮食组的雄性大鼠,研究了注射1,2 - 二甲基肼(DMH)后的肿瘤发生率。每组20只喂食不同饮食的大鼠,在最初24周每周腹腔注射DMH(15毫克/千克体重/周),另外20只注射生理盐水。在实验第28周后对96只注射DMH的大鼠进行尸检,其中88只在实验的第32周或最后一周进行尸检。喂食15%和22.5%膳食蛋白质的大鼠,其小肠和大肠腺癌更大且数量显著更多。在喂食22.5%蛋白质的注射DMH大鼠中,在第21周首次观察到外耳道皮脂腺产生角蛋白的乳头状瘤。随后在所有DMH处理组的一些大鼠中也观察到了这些肿瘤。随着时间推移,所有组的耳部肿瘤大小和数量都有所增加,但发生率最高的是喂食22.5%蛋白质的组。注射生理盐水的大鼠未观察到肿瘤。添加尿素并未增加肿瘤数量,也未导致结肠或盲肠内容物的pH值、脲酶活性或氨浓度以及血液胆固醇发生变化。随着膳食蛋白质增加,盲肠氨浓度升高,而结肠和盲肠pH值下降。门静脉血尿素和胆固醇随着膳食蛋白质增加而升高。DMH处理的大鼠结肠和盲肠氨浓度显著更高,血液胆固醇更低。尽管喂食7.5%蛋白质的大鼠在喂食0至6周期间体重增加显著较少,但在6至26周期间体重增加显著更高。在16周进行尸检的大鼠中未发现肿瘤。

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