Yuhas J M, Davis M E, Glover D, Brown D Q, Ritter M
Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):519-22. doi: 10.1016/0360-3016(82)90674-5.
In attempting to account for the ability of most solid tumors to restrict the absorption of WR-2721, aminopropyl-aminoethylphosphorothioate, we examined a number of drug characteristics which might allow for this restriction, and observed that drug hydrophilicity was a major contributing factor. When the highly hydrophilic WR-2721 was dephosphorylated, the drug became less hydrophilic and could readily cross tumor cell membranes. In addition, conventional radioprotectants, such as cysteine and mercaptoethylamine, were shown to be less hydrophilic than WR-2721 and also to cross tumor membranes readily. Therefore, drug hydrophilicity would appear to be the factor underlying the ability of WR-2721 to selectively protect normal tissues while most other protectors alter the radiation resistance of normal and tumor tissue alike. A red blood cell model for studying this problem in greater detail is described.
在试图解释大多数实体瘤限制WR-2721（氨丙基-氨乙基硫代磷酸酯）吸收的能力时，我们研究了一些可能导致这种限制的药物特性，并观察到药物亲水性是一个主要因素。当高度亲水性的WR-2721被去磷酸化时，该药物的亲水性降低，并能够轻易穿过肿瘤细胞膜。此外，传统的辐射防护剂，如半胱氨酸和巯基乙胺，被证明比WR-2721亲水性更低，并且也能轻易穿过肿瘤细胞膜。因此，药物亲水性似乎是WR-2721能够选择性保护正常组织，而大多数其他防护剂却同等程度改变正常组织和肿瘤组织辐射抗性这一能力背后的因素。本文描述了一个用于更详细研究该问题的红细胞模型。
