Studies on the mechanism of the selenite-induced decrease in cell attachment: effect of selenite on the levels of...

We previously reported that exposure of HeLa cells to selenite for 2 h results in a decrease in their ability to attach to fibronectin (Yan and Frenkel, Cancer Res. 52, 5803-5807 [1992]), as well as a decrease in the level of fibronectin receptor (alpha5beta1 integrin) at the cell surface (Yan and Frenkel, Biol. Trace Element Res. 46, 79-89 [1994]). We have now found that after exposure to selenite, there was a decrease in the total cellular content of the receptor protein, as well as in the level of the mRNAs for both of the subunits. Exposure of cells to actinomycin D (an inhibitor of RNA synthesis) also resulted in a decrease in the level of these mRNAs, suggesting that the effect of selenite is the result of its known inhibitory effect on RNA synthesis (Frenkel, Toxicol. Lett. 25, 219-223 [1985]). Exposure of cells to actinomycin D for 2 h also resulted in a decrease in the ability of cells to attach to fibronectin. Furthermore, both selenite and actinomycin D caused a decrease in integrin mRNA levels and in cell attachment to fibronectin only when high-density cells were exposed to the agents. In contrast, when low-density cells were exposed,neither agent had any detectable effect on mRNA levels or on cell attachment. These results have suggested the following scheme for the mechanism of the inhibition of cell attachment by selenite: After exposure to selenite for 2 h, there is a significant inhibition of cellular RNA synthesis, which results in a general decrease in the cellular level of those mRNAs with relatively short half-lives, including in particular those of the fibronectin receptor. This leads to a decrease in the intracellular level of the receptor protein and, consequently, in its level at the cell surface, which in turn causes a decrease in the rate of cell attachment to fibronectin.