title: Elimination of potential mutagenicity in platelet concentrates that are virally inactivated with psoralens and ultraviolet A light.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that hydrophobic resin adsorption of PUVA-treated PCs will conveniently remove functional psoralens and eliminates their mutagenic potential.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, USA.
authors.forename: H
authors.initials: H
authors.lastname: Margolis-Nunno
authors.forename: R
authors.initials: R
authors.lastname: Robinson
authors.forename: E
authors.initials: E
authors.lastname: Ben-Hur
authors.forename: S
authors.initials: S
authors.lastname: Chin
authors.forename: T
authors.initials: T
authors.lastname: Orme
authors.forename: B
authors.initials: B
authors.lastname: Horowitz
mesh_terms: D000327:Adsorption; D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects / Q000821:virology*; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D017713:Platelet Transfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012116:Resins, Plant; D014307:Trioxsalen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D009153:Mutagens; D012116:Resins, Plant; D004247:DNA; C018822:aminomethyltrioxsalen; D014307:Trioxsalen