INHIBITION OF THYMIDINE KINASE IN CULTURED MAMMARY-TUMOR CELLS BY THECHEMOPREVENTIVE ORGANOSELENIUM COMPOUND, 1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE

To identify mechanisms by which the organoselenium compound 1,4-phenyl enebis(methylene)selenocyanate (p-XSC) mediates its chemopreventive ac tivities, we have examined its effects on cell lines derived from brea st cancer of humans and rats. When log-phase cells were treated with a dose of 1 mu Mp-XSC, we observed a significant decrease in thymidine kinase (TK) activity within 4 h, and reduced thymidine incorporation a fter 24-48 h. When the dose of p-XSC was increased to 2 mu M, the decr ease in TK was accompanied by a modest, but significant, decrease in t hymidine incorporation at 4 h, and a greater inhibition after 24-48 h. At a dose of greater than or equal to 3 mu M, we observed a large dec rease in TK, accompanied by >70% reduction in thymidine incorporation, as well as decreases in mitochondrial activity and cell numbers, all within 4 h. Equal concentrations of selenium in the form of Na2SeO3 ha d no effect on the parameters described above. These data suggest that inhibition of thymidine kinase is an early effect of p-XSC in culture d breast tumor cells.