Virus sterilization in platelet concentrates with psoralen and ultraviolet A light in the presence of quenchers.
The virucidal and functional effect of the treatment of platelet concentrates (PCs) with long-wave ultraviolet light (UVA) and the psoralen derivative 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) was studied. Cell-free vesicular stomatitis virus (VSV) was completely inactivated (greater than or equal to 6.5 log10) on treatment of PCs with 25 micrograms per mL (85 microM) of AMT and with 20.7 J per cm2 (30 min) of UVA in the presence of air, or with 82.8 J per cm2 (2 hours) of UVA under conditions of reduced oxygen tension. When treatment was in air, the extent and rate of platelet aggregation in response to collagen measured after overnight storage were reduced to about 70 and 50 percent of control values, respectively; however, aggregation responses were similar to those of controls when PCs were treated under reduced oxygen tension. As a means of eliminating the necessity of oxygen depletion during AMT and UVA treatment, we examined the effects of the addition of quenchers of reactive oxygen species. The presence of 2 mM (2 mmol/L) mannitol during treatment of PCs with 25 micrograms per mL of AMT and 20.7 J per cm2 of UVA in air significantly improved the aggregation response and other in vitro indicators of platelet function and had little or no effect on VSV inactivation. Less benefit was observed with the other quenchers examined. Thus, the nucleic acid specificity of psoralen photoinactivation under reduced oxygen conditions may also be attainable when selected free radical scavengers such as mannitol are present during treatment in air.
Margolis-Nunno
H
H
New York Blood Center, New York.
Williams
B
B
Rywkin
S
S
Geacintov
N
N
Horowitz
B
B
D001792:Blood Platelets / Q000382:microbiology*; D016166:Free Radical Scavengers; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D011701:PUVA Therapy; D010974:Platelet Aggregation / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects*
D016166:Free Radical Scavengers; D008353:Mannitol