RNA-PROTEIN CROSS-LINKS INDUCED BY SENSITIZATION WITH A PYRROLOQUINOLINONE DERIVATIVE, A FUROCOUMARIN ANALOG

The capacity of 2,6-dimethyl-9-methoxy-4H-pyrrolo [3,2,1-ij] quinolin- 4-one (PQ), a furocoumarin analogue, of inhibiting protein synthesis i n Ehrlich cells upon UVA irradiation was investigated. Using 8-methoxy psoralen (8-MOP) as a reference, we observed that in our short-term te st the block of RNA synthesis do not affect protein synthesis, which i s driven by pre-synthesised molecules of m-RNA; actually 8-MOP, studie d at 100 mu M concentration, practically abolished RNA synthesis witho ut affecting significantly protein synthesis. Studying PQ sensitizatio n in HL60 cells by alkaline elution and protein precipitation, the for mation of covalent RNA-protein cross-links was observed. 8-MOP, assaye d in severe experimental conditions, induced only moderate amounts of such lesion. On the basis of the data obtained in experiments carried out using various scavengers or exposing cells to UVA light in a nitro gen atmosphere, this damage appeared to be due to singlet oxygen forma tion, which is generated by PQ to a large extent. These results are co nsistent with the data obtained by H. Singh and J.A. Vadasz (Singlet o xygen: a major reactive species in the furocoumarin photosensitized in activation of E.coli ribosomes, Photochem. Photobiol., 28 (1978) 539-5 45) on E.coli ribosomes. The lower activity we observed with 8-MOP mig ht be attributed to a different sensitivity of whole mammalian cells i n comparison with isolated ribosomes. (C) 1997 Elsevier Science S.A.