To explore cellular effects of potent organoselenium chemopreventive agents we have used a rat mammary tumor cell line. We demonstrate that 1,4-phenylenebis(methylene) selenocyanate (p-XSC) at a dose of 5 microM is a more potent inhibitor of DNA, RNA and protein synthesis as well as of mitochondrial transmembrane potential than its chemopreventive counterparts benzyl selenocyanate (BSC) and sodium selenite. These differences were also reflected in reduced growth rate by 24 and 48 hr. Cell-cycle and cell-morphology analysis revealed that higher doses of p-XSC (10 microM) caused DNA fragmentation which was accompanied with partial loss of nuclear stainability, whereas BSC caused a noticeable change in cell-cycle distribution and extensive micronucleation. Overall, our results point to cellular targets of selenium compounds which may mediate their chemopreventive activities in mammary tissues.