Skin photosensitization and cross-linkings formation in native DNA by furocoumarins.

Furocoumarins (psoralens) are a well known group of substances which show interesting photo­ sensitizing properties on several biological sy­ stems 1_<; the best known of these effects in sensiti­ zation of human and guinea-pig skin 2; 4’ 8> 9, in the production of which the various furocoumarin deri­ vatives show very different activities. At present the photosensitizing effects of furo­ coumarins are attributed to their photobinding to DNA. These compounds photoreact with pyrimidine bases of native DNA forming both monofunctional photoadducts and bifunctional ones (cross-linkages). At this point the question arises if monofunctio­ nal adducts and cross-linkings are or not equally effective in producing the skin-photosensitization. In this respect, the data obtained by Cole 10 study­ ing the inactivation of Escherichia coli and bacterio­ phage I by irradiation in the presence of psoralen stressed the greater importance of cross-linkages. In past time, we have determined the initial rate constants of the total photobinding of several furo­ coumarin derivatives to DNA, without distinguish­ ing the types of adducts formed n . Working with a small number of furocoumarins, we had found that the skin-photosensitizing potency of the various derivatives correlated well with their photobinding ability with DNA. Successively, however, by extend­ ing these studies to a larger group of furocouma­ rins, in particular to several methyl-derivatives of psoralen, this correlation was found to be no more p resen t12. We have now determined for the photoreactions between several furocoumarins and native DNA the rate constant values of the cross-linkages formation.