The possible formation of
singlet oxygen via photoexcited
psoralens has been associated with the occurrence of, amongst others,
erythema. Therefore it has been suggested to combine PUVA with the topical or systemic administration of
antioxidants. However, the effect of these
antioxidants on the photobinding of
psoralens to
DNA, which is held responsible for the anti-proliferative effect, should be taken into account. In the present study the effect of two phenolic
antioxidants,
alpha-tocopherol (AT) and
butylated hydroxytoluene (
BHT), on the in vivo photobinding of
8-methoxypsoralen (8-MOP) to not only epidermal
DNA, but also
proteins and
lipids was determined. After topical application of an ethanolic
antioxidant solution onto the shaven skin of Wistar rats, labeled
8-MOP was applied using the same
solvent. After this the rats were exposed to UV-A. By separating epidermal
lipids,
DNA/
RNA and
proteins by a selective extraction method, irreversible binding of
8-MOP to each of these biomacromolecules was determined. Both AT and
BHT caused a decrease in the photobinding of
8-MOP to epidermal
DNA and
proteins. To investigate the underlying mechanism of this protection, the effect of AT was compared with that of AT-
acetate. It also proved helpful to study the effects of the
antioxidants on the photobinding of another
photosensitizer, namely
chlorpromazine. From these experiments it was concluded that AT and
BHT affect
8-MOP photobinding by quenching reactive
8-MOP intermediates, involving the phenolic
hydroxyl group of the
antioxidants.
BHT offered protection against
lipid binding of
8-MOP but AT, especially at high concentrations, enhanced the UV-A-induced binding of
8-MOP to
lipids.(ABSTRACT TRUNCATED AT 250 WORDS)