INDUCTION IN HUMAN-SKIN FIBROBLASTS OF SISTER-CHROMATID EXCHANGES (SCES) BY PHOTOADDITION OF 2 NEW MONOFUNCTIONAL PYRIDOPSORALENS IN COMPARISON TO 3-CARBETHOXYPSORALEN AND 8-METHOXYPSORALEN

The induction of SCEs [sister chromatid exchanges] in human fibroblasts by photoaddition of a pyrido[3,4-c]psoralen (PyPs) and its 7-methyl derivative (MePyPs), 2 newly synthesized monofunctional agents proposed for photochemotherapeutic use, was compared to that of another monofunctional agent, 3-carbethoxypsoralen (3-CPs) and to the bifunctional compound, 8-methoxypsoralen (8-MOP). The yield of SCEs/cell and of SCEs/chromosome was determined at equimolar concentrations (10-6 M) of all the drugs with increasing doses of 365 nm radiation (UVA). In the dark, the drugs alone had either no effect (8-MOP, PyPs) or a very slight effect (3-CPs, MePyPs). Nor did UVA alone demonstrate at inducing action (14.4 kJ/m2). With all the agents the average frequencies of SCE increased with increasing UVA doses, reaching a plateau level for the monofunctional compounds. The order of effectiveness for the linear part of the induction curves was MePyPs > PyPs > 8-MOP .mchgt. 3-CPs, whereas at the maximal level the order was 8-MOP > PyPs > MePyPs > 3-CPs. Determination of the frequencies of 2nd generation mitosis indicates that MePyPs is the most cytotoxic. The results focus the attention on the importance of the structure of psoralen monoadducts which, for certain genetic endpoints, might be as efficient as cross-links.