Spectral effects in activation of the human immunodeficiency virus promoter by psoralens plus ultraviolet A treatment.
The effects of PUVA treatment on HIV promoter activation and cell killing in HIV cat/HeLa cells were studied using two UV sources, a UVASUN sunlamp and a UVAR Photoactivation Chamber. A 4 to 5 times higher dose of ultraviolet radiation was required from the UVASUN lamp than from the UVAR lamps: 1) to activate the HIV promoter in the presence of 0.1 or 1.0 microgram/ml 8-MOP and 2) to reduce cell survival to a level of 10%, in the presence of 0.1 or 1.0 microgram/ml 8-MOP. In addition, exposures performed with a fixed dose of 20 kJ/m2 at varying concentrations of 8-MOP, required a 4.7 times higher combined PUVA dose from the UVASUN lamp than from the UVAR lamps. Two possible sources of these differences were analyzed: (1) the presence of UVB + UVA2 (280-340 nm) in the radiation emitted by the UVAR, but not the UVASUN lamp, and its potential biological activity independent of 8-MOP, and (2) the difference in the overlap of the emission spectra of the two lamps with the absorption spectrum of 8-MOP. The area of overlap was higher for the UVAR lamp than for the UVASUN lamp by a factor of 4.6, which is close to the difference between these two lamps in induction of the HIV promoter and killing HeLa cells. This indicates that the effectiveness of a particular UVA source used in combination with 8-MOP can be predicted by its congruence to the absorption spectrum of the photosensitizing drug.
Miller
S A
SA
Center for Devices and Radiological Health, US Food and Drug Administration, Rockville, MD 20857.
Beer
J Z
JZ
Strickland
A G
AG
Zmudzka
B Z
BZ
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology*; D011701:PUVA Therapy; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000528:radiation effects*; D011829:Radiation Dosage; D014466:Ultraviolet Rays
D015500:Chloramphenicol O-Acetyltransferase; D008730:Methoxsalen