Interstrand crosslinks in DNA of phage lambda after exposure to 8-methoxypsoralen and trimethylpsoralen in the presence of light

Abstract

Two medically useful photosensitizing furocoumarins, 8-methoxypsoralen (8-MOP) and 4,5'8-trimethylpsoralen (TMP) were compared with respect to their abilities to produce interstrand crosslinks in DNA. DNA from bacteriophage lambda, labeled with 32P, was subjected to sedimentation in alkaline sucrose gradients following exposure to several concentrations of 1 of the 2 psoralens and irradiation (UV-A, 360 nm) for various times. In alkaline sucrose gradients, crosslinked DNA molecules sediment about 1.4 times faster than undamaged DNA strands and the proportion of molecules carrying crosslinks can be estimated with reasonable accuracy. At equimolar psoralen concentrations (2 x 10(-7)M, or 4 x 10(-5)M) and with increasing irradiation times, the rate of production of crosslinked DNA was 4 to 30 times greater for TMP than for 8-MOP. Differences in the therqpeutic efficacy of 8-MOP and TMP in various clinical situations may be accounted for by the types of photoadducts formed by each drug as well as by their solubilities, rates of absorption and rates of metabolic degradation.