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细胞毒素作用下小鼠骨髓中谷胱甘肽及谷胱甘肽转移酶水平的改变

Altered mouse bone marrow glutathione and glutathione transferase levels in response to cytotoxins.

作者信息

Adams K J, Carmichael J, Wolf C R

出版信息

Cancer Res. 1985 Apr;45(4):1669-73.

PMID:3978635
Abstract

The mouse bone marrow has been used as a model for the investigation of the response of cells to cytotoxins and carcinogens. The effects of cyclophosphamide, 1-beta-D-arabinofuranosylcytosine, and X-irradiation on the levels of glutathione and glutathione transferases have been studied. A high dose of cyclophosphamide (500 mg/kg) caused a significant depletion of glutathione levels in marrow, liver, and blood. A lower dose, 75 mg/kg, caused a similar depletion but only in marrow and liver. In this case, 5 to 7 days following treatment, the glutathione content of surviving cells was 1.8- to 3-fold higher than in controls. Glutathione transferase activity was also increased at this time (2- to 3-fold). 1-beta-D-Arabinofuranosylcytosine and X-irradiation also caused a depletion of marrow glutathione and glutathione transferase levels followed increased cellular levels (approximately 2-fold) 3 to 4 days later. Animals given cyclophosphamide (75 mg/kg) survived an otherwise lethal dose of this compound administered 5 to 7 days later. The time course of this effect closely paralleled the higher glutathione and glutathione transferase levels, suggesting a correlation between these effects.

摘要

小鼠骨髓已被用作研究细胞对细胞毒素和致癌物反应的模型。研究了环磷酰胺、1-β-D-阿拉伯呋喃糖基胞嘧啶和X射线照射对谷胱甘肽及谷胱甘肽转移酶水平的影响。高剂量环磷酰胺(500mg/kg)导致骨髓、肝脏和血液中谷胱甘肽水平显著降低。较低剂量75mg/kg也导致类似的降低,但仅在骨髓和肝脏中。在这种情况下,治疗后5至7天,存活细胞的谷胱甘肽含量比对照组高1.8至3倍。此时谷胱甘肽转移酶活性也增加(2至3倍)。1-β-D-阿拉伯呋喃糖基胞嘧啶和X射线照射也导致骨髓谷胱甘肽和谷胱甘肽转移酶水平降低,随后在3至4天后细胞水平升高(约2倍)。给予环磷酰胺(75mg/kg)的动物在5至7天后能够耐受该化合物的致死剂量。这种效应的时间进程与较高的谷胱甘肽和谷胱甘肽转移酶水平密切平行,表明这些效应之间存在相关性。

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