Elimination of potential mutagenicity in platelet concentrates that are virally inactivated with psoralens and ultraviolet A light.
Elimination of potential mutagenicity in platelet concentrates that are virally inactivated with psoralens and ultraviolet A light.
复制标题
消除用补骨脂素和紫外线 A 光灭活病毒的血小板浓缩物中潜在的致突变性。
DOI：
10.1046/j.1537-2995.1995.351096026368.x
复制
发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Horowitz,B
中科院分区：
文献类型：
--
作者：
Margolis-Nunno,H;Robinson,R;Ben-Hur,E;Chin,S;Orme,T;Horowitz,B
背景技术背景：对于血小板浓缩物（PC）的病毒灭菌，使用氨甲基三甲基补骨脂素（AMT）和长波紫外线A（UVA）进行处理已显示出有效性。研究发现，在0.35 mM芦丁存在下，用50 μ g/mL AMT和38 J/cm 2 UVA处理可有效杀死病毒，同时保持血小板完整性。然而，有关于peptiens和UVA（PUVA）处理的PCs.Study设计和方法的潜在致突变性的关注：PUVA处理的PC与含有C18作为配体的疏水性树脂的吸附用于AMT去除，这是通过使用放射性AMT定量。检查PUVA处理的PC（有和无C18处理）的溶液pH值和对激动剂的血小板聚集反应。此外，剩余的AMT活性测定AMT的杀病毒活性或纳入细胞DNA后，第二次UVA照射和其致突变潜力在艾姆斯test.Results：PUVA治疗后的PC，残留的AMT保留杀病毒和加合物形成能力后，再暴露于UVA，但活动比原来观察到的。如先前所发现的，AMT与大鼠肝S9微粒体酶在黑暗中孵育后具有致突变潜力。PUVA治疗将这种潜力降低了90%。PUVA治疗后的C18吸附对血小板完整性没有负面影响，并消除了50%的放射性AMT。此外，AMT处理的PC的所有可检测到的杀病毒、核酸修饰和致突变活性均被C18去除。结论：PUVA处理的PC的疏水树脂吸附可方便地去除功能性致突变物并消除其致突变潜力。
BACKGROUND: For virus sterilization of platelet concentrates (PCs), treatment with aminomethyltrimethyl psoralen (AMT) and long‐wavelength ultraviolet A light (UVA) has shown efficacy. It has been found that treatment with 50 micrograms per mL of AMT and 38 J per cm2 of UVA in the presence of 0.35‐mM rutin efficiently kills viruses while maintaining platelet integrity. There is, however, concern about the mutagenic potential of psoralens and UVA (PUVA)‐treated PCs.STUDY DESIGN AND METHODS: Adsorption of PUVA‐treated PCs with a hydrophobic resin containing C18 as the ligand was used for AMT removal, which was quantitated by the use of radioactive AMT. PUVA‐treated PCs, with and without C18 treatment, were examined for solution pH and platelet aggregation response to agonists. In addition, residual AMT activity was determined by AMT's virucidal activity or incorporation into cellular DNA upon a second UVA irradiation and by its mutagenic potential in the Ames test.RESULTS: After PUVA treatment of PCs, residual AMT retained virucidal and adduct‐forming ability upon re‐ exposure to UVA, but activities were less than those observed originally. As has been found previously, AMT had mutagenic potential following incubation in the dark with rat liver S9 microsomal enzymes. The PUVA treatment reduced this potential by 90 percent. C18 adsorption following PUVA treatment had no negative effect on platelet integrity and eliminated 50 percent of the added radioactive AMT. In addition, all detectable virucidal, nucleic acid‐modifying, and mutagenic activities of AMT‐treated PCs were removed by C18.CONCLUSION: These results suggest that hydrophobic resin adsorption of PUVA‐treated PCs will conveniently remove functional psoralens and eliminates their mutagenic potential.