Genotoxic Effects of Psoralen
The widespread use of psoralen plus UV light therapy for the treatment of skin disorders has focused attention on the possible genotoxic effects of this treatment. The simultaneous damage to both strands of the DNA duplex produced by psoralen cross-links poses a greater genetic risk than the more limited involvement of monoadducts on only one strand. The comparison of the mutagenic potential of various monofunctional furocoumarins has as an additional goal the development of photochemotherapeutic agents with high photoactivity but lower genotoxicity than 8-methoxypsoralen or 4,5',8-trimethylpsoralen. Psoralen photoreaction has been shown to induce chromosome aberrations in vitro in human lymphocytes, Chinese hamster ovary cells, and mouse lymphoma cells. The relative efficiencies of monoadducts and cross-links in recombinogenesis have been studied by comparing mono- and bifunctional furocoumarins, as well as by split-dose experiments with cross-linking psoralens. Recombinational repair plays a major role in the cellular response to psoralen photoreaction, particularly interstrand cross-links.