MODULATION OF 8-METHOXYPSORALEN-DNA PHOTOADDUCT FORMATION BY CELL-DIFFERENTIATION, MITOGENIC STIMULATION AND PHORBOL ESTER EXPOSURE IN MURINE T-LYMPHOCYTES

The effects of cell differentiation and mitogen and phorbol ester stim ulation on the formation of 8-methoxypsoralen (8-MOP)-DNA photoadducts in murine T lymphocytes were examined using H-3-8-MOP. While there we re no significant differences in 8-MOP photoadduct formation among BAL B/c thymocytes, splenocytes, splenic T cells and MRL/lpr lymph node ce lls, BALB/c bone marrow cells showed fewer photoadducts than did the l ymphocytes. This suggested that proliferating progenitor cells may be resistant to 8-MOP photoadduct formation. Incubation of purified splen ic T cells with lectin mitogens for 2 h or with phorbol 12-myristate 1 3-acetate (PMA) for 2-43 h resulted in reduction of 8-MOP photoadduct formation in the DNA, whereas 64 h cultivation with these agents augme nted the photoadduct formation. The reduction of photoadduct formation induced by phytohemagglutinin was restored by the further addition of a protein kinase C (PKC) inhibitor, H-7, to the culture. Thus, it is assumed that the reduction of adduct formation evoked by mitogens and PMA is mediated in part by the activation of PKC in the cells. On the other hand, the augmentation of the adduct formation induced by the lo nger-period cultures with mitogens and PMA appeared to be caused by do wn-regulation of PKC. The present study showed that the stimulatory si gnals in which PKC is presumably involved affect the ability of cells to form s-MOP-DNA photoadducts.