INHIBITION OF DNA SYNTHESIS BY PSORALEN‐INDUCED LESIONS IN XERODERMA PIGMENTOSUM AND FANCONI'S ANEMIA FIBROBLASTS

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Abstract
Abstract— Exposure of human cells to psoralens and near‐UV light produces a mixture of monoadducts and crosslinks in DNA, which inhibit DNA synthesis by blocking replicon initiation and chain elongation. 8‐Methoxypsoralen (8‐MOP) has a greater effect than angelicin in normal, xeroderma pigmentosum, and Fanconi's anemia cells. Recovery of DNA synthesis is not detectable up to 8 h after exposure. The average distance between lesions that block replication in individual replicons was measured by means of bromodeoxyuridine photolysis. After exposure to 10 μg/mℓ of 8‐MOP and 7500 J/m2 of near‐UV light, blocks were formed every 20 μm. Replicon initiation was inhibited by exposure to near‐UV light alone in normal and xeroderma pigmentosum. Exposure to low concentrations of angelicin or 8‐MOP plus near‐UV light inhibited replicon initiation in normal and Fanconi's anemia cells, but not in xeroderma pigmentosum cells. Inhibition of initiation was not obvious after treatment with high concentrations of 8‐MOP or angelicin because of the dominant effect of crosslinks in blocking chain elongation.