The furocoumarin photosensitizing effect on the virus-producing Graffi leukaemia cells.

We have previously reported 1 that cells of the Graffi leukaemia, an experimental tumor of the mouse, irradiated with long wave UV light in the presence of skin-photosensitizing furocoumarins (psoralens), lose their tumor-transmitting capacity when transplanted into adult mice. This result can be explained by the C4-photocycloaddition that these drugs yield to the pyrimidine bases of DNA and R N A 2-5, with formation of covalent linkages; in addition, in the double-stranded DNA inter-strand cross-linkages occur 6. Therefore, it may be foreseen that this photochemical interaction might interfere strongly with the macromolecular synthesis as pre­ vious observed in other cell lines 7~9. These cells contain and produce the Graffi virus, an oncogenic RNA tumor v iru s10; actually, the leukaemia is also transferable by injecting cell-free filtrates into newborn mice n . Moreover, while some aspects only of the furocoumarin photosensibiliza­ tion on a living cell are still not yet clear, the ef­ fects on the Graffi virus properties as well on the virus-cell interactions, i. e. the infecting and trans­ forming ability or the capacity of the cell to pro­ duce new viruses, are entirely unknown. Thus, in this paper we have studied the furo­ coumarin photosensitizing effect on the Graffi virus­ cell system, using psoralen, the parent compound of natural origin, and 8 -methylpsoralen and 4 ,4 ',8trimethylpsoralen, two synthetic products, all three drugs with strong photosensitizing activity.