EFFECTS OF CHEMOPREVENTIVE SELENIUM-COMPOUNDS ON JUN N-KINASE ACTIVITIES

Activation of Jun-N-kinases (JNK) is stimulated by diverse agents incl uding UV-irradiation, heat shock, tumor necrosis factor and osmotic sh ock. In the present study we have elucidated the effect of the organos elenium chemopreventive agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC), on UV-mediated JNK activation. Using mouse fibroblasts as a model cell system we found that low concentrations (1-10 mu M range) o f p-XSC did not affect JNK activity, yet were capable of potentiating JNK activity when administered prior to UV-irradiation, While higher d oses of p-XSC have minimal effect on JNK activation, when combined wit h UV, there is a dose-dependent decrease in JNK activation, Similar to its effects on JNK, p-XSC is a potent inducer of src-related tyrosine kinases. p-XSC mediated changes in JNK activation correlate with its ability to potentiate the association of JNK with p21(ras), in a manne r similar to that we have previously observed with GTP or sodium vanad ate, That p-XSC can modulate JNK activities points to a possible mecha nism by which it contributes to the cell's ability to cope with stress .