SKIN‐PHOTOSENSITIZING FUROCOUMARINS: PHOTOCHEMICAL INTERACTION BETWEEN DNA AND —O¹⁴CH₃ BERGAPTEN (5‐METHOXY‐PSORALEN)

Abstract

For some years the mechanism of the photosensitizing effects displayed by some furocoumarins on various biological substrates (human and guinea-pig skin, bacteria cultures, mammalian cells adapted to in vitro growth, viruses) have been studied. Recently it has been pointed out that a photoreaction occurs between the photosensitizing furocoumarins and DNA after irradiation at 3655 A. By use of a labeled furocoumarin, i.e.-O"CH, bergapten or 5-methoxy-psoralen, this has been confirmed and more extensively studied. During the irradiation a stable combination of the furocoumarin with native DNA takes place with a quantum yield of 5.2 x lo-*. It is probable that the reactive sites of DNA are the pyrimidine bases. Yeast-RNA and the same DNA after heat-denaturation or in the presence of high NaCl concentration photoreact at a much reduced rate. This photoreaction may explain some various biological photosensitizing effects produced by furocoumarins. I N T R O D U C T I O NTHE FUROCOUMARINS, or psoralens, have been extensively studied in this and by American since some of these substances (mainly psoralen and various methyl-derivatives, xanthotoxin or 8-methoxy-psoralen, bergapten or 5-methoxy-psoralen, among others) have a photosensitizing action on the human or guinea-pig skin, i.e. they induce erythema followed by pigmentation. They act also, upon irradiation at 3655 A, on cultures of microorganism, with a letha1(7.8) and mutagenic on the mammalian cells adapted to in vitro growth with the formation of giant cells,(lO) and they inactivate DNA-containing viruses. (11)In continuing our investigation of the mechanism of action of the skin-photosensitizing furocoumarins, we have recently reported(llJ2) studies on the interaction between these substances and deoxyribosenucleic acid (DNA).We have pointed out that all furocoumarins, both skin-photosensitizing and inactive, have the capacity of binding in darkness to DNA and, to a much less extent, to RNA.('')After irradiation of an aqueous solution of DNA and a skin-active furocoumarin at 3655 A, we have observed strong modifications in the fluorescence spectra of the solutions, whereas in the presence of skin-inactive substances the spectra remained unchanged. (12)

Induction of Phenylalanine Ammonia Lyase and Pisatin by Photosensitive Psoralen Compounds

“…The photochemistry of furocoumarins (psoralens) has received considerable attention from several groups of workers (2,10,11,19). The parent compound, psoralen, and some of its derivatives have a photosensitizing action on viruses (3,12), bacterial cells, and mammalian cultures (2,13) and produce lethal and mutagenic effects.…”

“…The in vitro specificity of activated mitomycin C for double-stranded DNA has been established; however, it reacts nearly as well with RNA (24). In contrast, psoralens, upon irradiation with 360 nm light, bind primarily to native DNA (11,14). Also, the products formed by irradiation of psoralen with the DNA components, thymine and cytosine, have been isolated and characterized ( Fig.…”

Structure specificity of polydeoxyribonucleotides for the photoreaction with psoralen

“…Psoralen and other furocoumarins photoreact with pyrimidine bases of DNA, bot in vitro and in vivo [1][2][3][4][5][6][7][8], under irradiation at long wavelength ultraviolet light. A C4-cycloaddition to the 5,6-double bond of pyrimidine bases occurs: furocoumarins can photoreact either with their 3,4-or 4',5'-double bond, forming therefore two types of photoadducts.…”

Photosensitizing Effect of Trisoralen on DNA Synthesis in Human Cells Grownin Vitro

“…They are also used to increase the tolerance of human skin to solar radiation (Fitzpatrick, Arndt, E1 Mofty and Pathak 1966, Imbrie, Daniels, Bergeron, Hopkins and Fitzpatrick 1959, and El Mofty 1968. Musajo, Rodighiero, Breccia, Dal'Acqua and Malesani (1966), Musajo and Rodighiero (1970) and Pathak and Kramer (1969) have shown that 4,5',8-trimethylpsoralen (trisoralen, trixsalen) form a stable C4-cycloaddition product to DNA in aqueous solutions as well as in epidermal cells after longwavelength ultra-violet irradiation. Experiments reported in this study were designed to determine how this trisoralen photoproduct on the DNA molecule might lead to the many biological manifestations of furocoumarin photosensitization.…”