Vos O, Budke L, Grant G A
Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Nov;30(5):433-48. doi: 10.1080/09553007614551251.
In tissue culture, protection against X-irradiation by a number of cysteamine derivatives was studied and the results were compared with data obtained in mice. Compounds with a covered SH group, like WR 638, cysteamine phosphate, WR 2721, and AE 48527, showed practically no protection when dissolved in tissue-culture medium, but developed a protective activity when dissolved in rat blood. Thiol measurements demonstrated that in rat blood the compounds were partly hydrolysed to thiols. C511 was also hydrolysed in culture medium and was slightly less effective than cysteamine in culture medium. Cysteamine phosphate was hydrolsed more easily than cysteamine sulphate and the protective activity in rat blood was better. WR 2721 was also partly hydrolysed in rat blood. The in vitro protection of this compound was disappointing when compared with results in vivo. Its SH form (WR 1065) also showed less protection than expected from in vivo experiments. Thus, the little protection by WR 2721 in vitro in rat blood is not only due to its incomplete conversion into its thiol. Longer incubation times and the use of rat blood as a solvent brought the protective activity of WR 1065 almost up to the level of cysteamine. This may indicate that WR 1065 penetrates the cells poorly. WR 1065 was the only compound we studied whose protective activity in vitro was improved appreciably by dissolving it in rat plasma.
在组织培养中，研究了多种半胱胺衍生物对X射线照射的防护作用，并将结果与在小鼠身上获得的数据进行了比较。具有被保护的SH基团的化合物，如WR 638、磷酸半胱胺、WR 2721和AE 48527，当溶解在组织培养基中时几乎没有防护作用，但溶解在大鼠血液中时则表现出防护活性。硫醇测量表明，在大鼠血液中这些化合物部分水解为硫醇。C511在培养基中也会水解，其在培养基中的效果略逊于半胱胺。磷酸半胱胺比硫酸半胱胺更容易水解，在大鼠血液中的防护活性更好。WR 2721在大鼠血液中也会部分水解。与体内结果相比，该化合物的体外防护作用令人失望。其SH形式（WR 1065）的防护作用也低于体内实验的预期。因此，WR 2721在大鼠血液中的体外防护作用微弱不仅是由于其未完全转化为硫醇形式。更长的孵育时间以及使用大鼠血液作为溶剂使WR 1065的防护活性几乎达到半胱胺的水平。这可能表明WR 1065对细胞的穿透性较差。WR 1065是我们研究的唯一一种将其溶解在大鼠血浆中可显著提高其体外防护活性的化合物。
