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After irradiation at 3655 A of an aqueous frozen solution containing thymine and psoralen, a new photocompound was isolated by column chromatography. It contains a furocoumarin and a pyrimidinemoiety linked together by the formation of a cyclobutane ring (see formulas I1 and IU). By irradiation at 2537 A in acetic acid solution, the photocompound breaks up again yielding psoralen and thymine. From an aqueous frozen solution containing cytosine and psoralen irradiated at 3655 A, an analogous photocompound was obtained, which, however, consists of the addition to psoralen of a uracil molecule, instead of a cytosine one (IV, V). It has been stated that the hydrolytic deamination of the cytosine moiety to the uracil one takes place during the working up of the photocompound in aqueous solution after irradiation. Substances with properties similar to those above were obtained from bergapten (5-methoxy-psoralen) and thymine, from psoralen and thymidine or thymidylic acid, irradiated at 3655 A.The new substances may be considered as model compounds in explaining the photoreactions which take place between the skin-photosensitizing furocoumarins and DNA upon irradiation at 3655 A.

Abstract— Among the natural or synthetic furocoumarins (psoralens) a group exists which has interesting biological properties, the best known of which is skin‐photosensitization. The mechanism of action has remained unclarified for a long time. Furocoumarins lack photooxidative properties; they act by a mechanism that does not require oxygen and are therefore different from photodynamic substances. Photosensitizing furocoumarins when irradiated at 365 nm react with nucleic acids to give a C4‐cyclo‐addition to the 5,6‐double bond of the pyrimidine bases engaging their 3,4‐ or 4‵,5‵‐double bond. Differences exist in the behaviour of the various furocoumarins; psoralen reacts equally well with native DNA, with denatured DNA and with RNA, whereas bergapten, xanthotoxin and 8‐methylpsoralen at room temperature react to a much greater extent with native DNA than with denatured DNA and with RNA. A temperature effect has also been observed. In the case of native DNA an intercalation, occurring in the dark, of furocoumarins between two adjacent base pairs of the double helix is suggested as the first step in the reaction. The photoreaction is not accompanied by breaks in the polynucleotide chain or by conformational modifications of the macromolecule. A parallelism was observed between the order of activity of the substances of this group for photoreaction with native DNA and for skin‐photosensitization. Ehrlich ascites tumor cells lose completely their capacity of transmitting the tumor after irradiation in the presence of psoralen, bergapten and xanthotoxin. By hydrolysis of DNA extracted from Ehrlich ascites tumor cells irradiated in the presence of psoralen a photoadduct between psoralen and thymine was isolated.

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