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利用肾移植供体的人肝微粒体,通过前致癌物在中国仓鼠细胞体外诱导染色体畸变和姐妹染色单体交换。

Use of human-liver microsomes from kidney-transplant donors for the induction of chromatid aberrations and sister-chromatid exchanges by means of pre-carcinogens in Chinese hamster cells in vitro.

作者信息

Thust R, Warzok R, Grund E, Mendel J

出版信息

Mutat Res. 1978 Sep;51(3):397-402. doi: 10.1016/0027-5107(78)90127-6.

Abstract

Samples of two human livers taken during operation of kidney donor patients were processed for microsome fractions and used for metabolization of cyclophosphamide (CP) and dimethylnitrosamine (DMN) in combination with the NADPH-generating system. Rat-liver microsomes were checked for comparison. Induction of chromatid aberrations and sister-chromatid exchanges in a newly isolated clone of Chinese hamster fibroblasts served as indicators of activity. Human S-9 fractions standardized on protein content showed strong variations of CP and DMN activation. Whereas liver microsomes of one patient (who also suffered from Gaucher's disease) were highly active for both pre-carcinogens and metabolized DMN at the same level as the uninduced rat-liver microsomes, the S-9 fraction from the second patient failed to activate CP, but was distinctly positive for DMN. It is suggested that samples of liver and other organs of renal transplant donors might be a practicable source of freshly prepared human microsome fractions usable in biochemical, genetic and carcinogenetic studies. Problems concerning the extrapolation of results are discussed.

摘要

在肾脏供体患者手术过程中采集的两份人类肝脏样本被处理成微粒体部分,并与NADPH生成系统结合用于环磷酰胺(CP)和二甲基亚硝胺(DMN)的代谢。同时检测大鼠肝脏微粒体作为对照。以新分离的中国仓鼠成纤维细胞克隆中的染色体畸变和姐妹染色单体交换诱导情况作为活性指标。以蛋白质含量标准化的人类S-9部分显示出CP和DMN激活的强烈差异。一名同时患有戈谢病的患者的肝脏微粒体对两种前致癌物均高度活跃,且代谢DMN的水平与未诱导的大鼠肝脏微粒体相同,而第二名患者的S-9部分未能激活CP,但对DMN呈明显阳性。建议肾脏移植供体的肝脏和其他器官样本可能是可用于生化、遗传和致癌研究的新鲜制备的人类微粒体部分的可行来源。讨论了有关结果外推的问题。

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