Effects of chemopreventive selenium compounds on Jun N-kinase activities.

Activation of Jun-N-kinases (JNK) is stimulated by diverse agents including UV-irradiation, heat shock, tumor necrosis factor and osmotic shock. In the present study we have elucidated the effect of the organoselenium 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 microM range) of p-XSC did not affect JNK activity, yet were capable of potentiating JNK activity when administered prior to UV-irradiation. While higher doses of p-XSC have minimal effect on JNK activation, when combined with 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 p21ras, in a manner similar to that we have previously observed with GTP or sodium vanadate. That p-XSC can modulate JNK activities points to a possible mechanism by which it contributes to the cell's ability to cope with stress.