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可移植性小鼠淋巴瘤中肝脏药物代谢酶的比较模式及其与染色体畸变的可能相关性:一项时间进程研究。

Comparative patterns of hepatic drug metabolizing enzymes and their possible correlation with chromosomal aberrations in transplantable murine lymphoma: a time course study.

作者信息

Sarkar A, Mukherjee B, Rana M, Chatterjee M

机构信息

Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.

出版信息

Cancer Invest. 1994;12(5):477-83. doi: 10.3109/07357909409021406.

Abstract

The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT), cytosolic glutathione-S-transferase (GSHT) activities, and major chromosomal aberrations were evaluated over various periods of time, following tumor transplantation in male Swiss Albino mice. Changes in the above markers were studied (1) to monitor the entire carcinogenic process and (2) to test the suitability of chemopreventive exposures in terms of phase and duration of tumor growth. The microsomal cyt. P-450 content and the UDPGT activity were significantly elevated (p < 0.01-0.001) from the early stages of tumor growth while the cytosolic GSHT activity reached its highest level (p < 0.01-0.001) only 10 days after tumor transplantation. During the later stages of tumor growth all the biotransforming enzyme activities showed a downhill trend, which was significantly lower than that of their normal counterparts (p < 0.01-0.001). The frequency of different chromosomal aberrations, which were of major structural, numerical, and physiological types, increased steadily throughout the entire length of the carcinogenic process (30 +/- 2 days).

摘要

在雄性瑞士白化小鼠进行肿瘤移植后的不同时间段,对肝微粒体细胞色素P-450(细胞色素P-450)、尿苷二磷酸葡萄糖醛酸基转移酶(UDPGT)、胞质谷胱甘肽-S-转移酶(GSHT)活性的诱导差异水平以及主要染色体畸变进行了评估。研究上述标志物的变化,一是为了监测整个致癌过程,二是为了从肿瘤生长的阶段和持续时间方面测试化学预防暴露的适用性。微粒体细胞色素P-450含量和UDPGT活性从肿瘤生长早期就显著升高(p<0.01 - 0.001),而胞质GSHT活性仅在肿瘤移植后10天达到最高水平(p<0.01 - 0.001)。在肿瘤生长后期,所有生物转化酶活性均呈下降趋势,显著低于其正常对应物(p<0.01 - 0.001)。不同类型的染色体畸变,包括主要的结构、数量和生理类型,在整个致癌过程(30±2天)中稳步增加。

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