PHOTOTOXIC EFFECTS OF FOUR PSORALENS ON L1210 CELLS. THE CORRELATION WITH DNA INTERSTRAND CROSS‐LINKING

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Abstract
—: L1210 mouse leukaemia cells were treated with psoralen [S‐methoxy‐(XMOP), 4,5′,8‐trimethyI‐(TMP), 4′‐hydroxymethyl‐4,5′,8‐trimethyl‐(HMT) or 4′‐amino‐ methyl‐4,5′,8‐trimethylpsoralen (AMT)] in combination with long wavelength ultraviolct irradiation (Λ∼ 365 nm). In order to investigate the relative photobiological activities of the psoralens, cell viability and DNA‐synthesis activity as well as psoralen‐DNA photoaddition and DNA interstrand cross‐linking were measured after the treatment. In all assays the activity ranking order was found to he: TMP > HMT > AM7 > 8MOP. Furthermore, a direct correlation between phototoxicity, psoralen induced DNA interstrand cross‐links and inhibition of DNA synthesis was indicated. Finally, psoralen uptake by the cells appears to be an important determinant for phototoxicity, whereas their DNA photoreactivity does not.