Photosensitized decontamination of blood with the silicon phthalocyanine Pc 4: no activation of the human immunodeficiency virus promoter.
Photochemical decontamination of red blood cell concentrates (RBCC) with the silicon phthalocyanine Pc 4 and red light is being studied to enhance the viral safety of blood transfusion. Recent reports indicate that treatments with radiation and various phototsensitizing agents can activate the promoter of human immunodeficiency virus (HIV). This raises the possibility that an inadequate, sublethal photochemical treatment of RBCC could induce HIV in latently infected cells. This question has been addressed using HeLa cells stably transfected with the chloramphenicol acetyl transferase gene under the control of the HIV promoter. In control studies, 8-methoxypsoralen (8-MOP) excited by UVA light caused activation of the HIV promoter in a dose- and time-dependent manner. At 0.1 microgram/mL of 8-MOP, maximal activation occurred with 18 J/cm2, 30 h after light exposure, With Pc 4 at 20 nM, over 90% of HeLa cells were killed after 24 h when exposed to 1 J/cm2 of red light. During that time interval and over a wide range of light doses no activation of the HIV promoter occurred. It is concluded that RBCC sterilization with Pc 4 and red light is unlikely to induce HIV production in latently infected cells.
Zmudzka
B Z
BZ
Food and Drug Administration, Center for Devices and Radiological Health, Rockville, MD, USA.
Strickland
A G
AG
Beer
J Z
JZ
Ben-Hur
E
E
D017848:Blood-Borne Pathogens; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008730:Methoxsalen / Q000494:pharmacology; D017646:Organosilicon Compounds / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012821:Silanes; D014466:Ultraviolet Rays
D007211:Indoles; D017646:Organosilicon Compounds; D012821:Silanes; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon; D015500:Chloramphenicol O-Acetyltransferase; D008730:Methoxsalen