Minchinton A I, Chaplin D J
B.C. Cancer Research Centre, Vancouver, Canada.
Int J Radiat Biol. 1991 Jun;59(6):1425-33. doi: 10.1080/09553009114551271.
Intravenous administration of the fluorescent DNA stain Hoechst 33342 to tumour-bearing mice was used to label cells proportionally to their proximity from the vasculature. Flow cytometry was used to sort cells from the tumour into populations based on their Hoechst 33342-derived fluorescence. The cell populations were then assayed for their glutathione (GSH) content and their radiosensitivity. Tumours from mice pretreated with buthionine sulphoximine (BSO) were compared with untreated animals. The major findings of this study suggest that the cellular GSH concentration within tumours decreases with distance from the vasculature, and that the GSH concentration within cells from all locations in the tumour can be depleted by enzymatically inhibiting its synthesis using BSO. This depletion of GSH resulted in a small degree of hypoxic radiosensitization of cells both distal and proximal to the vasculature.
给荷瘤小鼠静脉注射荧光DNA染料Hoechst 33342,以根据细胞与脉管系统的接近程度按比例标记细胞。使用流式细胞术根据Hoechst 33342产生的荧光将肿瘤细胞分选成不同群体。然后测定这些细胞群体的谷胱甘肽(GSH)含量及其放射敏感性。将用丁硫氨酸亚砜胺(BSO)预处理的小鼠的肿瘤与未处理的动物进行比较。这项研究的主要发现表明,肿瘤内细胞的GSH浓度随着与脉管系统距离的增加而降低,并且使用BSO通过酶促抑制其合成可以耗尽肿瘤中所有位置细胞内的GSH浓度。GSH的这种耗竭导致脉管系统远端和近端细胞出现一定程度的缺氧放射增敏。