Activation of the human immunodeficiency virus promoter by UVA radiation in combination with psoralens or angelicins.
The effects of mono- and bifunctional furocoumarins plus UVA radiation (PUVA and related treatments) on the human immunodeficiency virus-1 (HIV-1) promoter were studied using HeLa cells stably transfected with the chloramphenicol acetyl transferase gene under the control of the HIV-1 promoter. The experiments were performed with three psoralens (5-methoxypsoralen, 5-MOP; 8-methoxypsoralen, 8-MOP; and 4'-aminomethyl-4,8,5'-trimethylpsoralen, AMT) and four angelicins (angelicin; 4,5'-dimethylangelicin, 4,5'-DMA; 6,4'-dimethylangelicin, 6,4'-DMA; and 4,6,4'-trimethylangelicin, TMA). The drugs alone and UVA radiation alone showed no effect on the HIV promoter. However, when the cells were incubated with the furocoumarins at 0.1-40 micrograms/mL and then irradiated, the HIV promoter was activated in distinct fluence ranges, i.e. (1) no promoter activity was discernible at low fluences (e.g. at 0.1 microgram/mL of 8-MOP up to 100 kJ/m2), (2) as the fluence was increased, the promoter activity increased to reach a maximum (10-50-fold with respect to the unexposed samples), and (3) as the fluence was further increased, the promoter activity decreased. Similar (although shifted on the fluence scale) patterns were observed with either > 340-nm UVA radiation or with UVA radiation contaminated with a small amount of UVB radiation (typical for PUVA lamps). The effective fluences were inversely related to the drug concentration. Experiments with 5-MOP and 8-MOP indicated reciprocity of the drug concentration and radiation fluence. The HIV promoter response patterns were similar for monofunctional angelicins and bifunctional psoralens.(ABSTRACT TRUNCATED AT 250 WORDS)
Zmudzka
B Z
BZ
Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20857.
Strickland
A G
AG
Miller
S A
SA
Valerie
K
K
Dall'Acqua
F
F
Beer
J Z
JZ
D002470:Cell Survival / Q000528:radiation effects; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000528:radiation effects*; D014162:Transfection; D014466:Ultraviolet Rays
D011564:Furocoumarins; C011659:angelicin; D015500:Chloramphenicol O-Acetyltransferase