Inhibition of phytohaemagglutinin--induced lymphocyte transformation and mitosis by ethidium bromide.

The effect of ethidium bromide (EB) on phytohaemagglutinin (PHA) induced lymphocyte transformation and mitosis was evaluated by morphology and 3H-thymidine uptake. EB at low concentrations is known to specifically bind to mitochondrial DNA and selectively inhibit mitochondrial protein synthesis. However at these concentrations EB inhibited both transformation and mitosis. Electron micrographs of lymphocytes cultured with PHA showed mitochondria of normal structure with round, oval or elongated shapes, well-defined cristae and electron dense matrix. However micrographs of PHA stimulated lymphocytes cultured with EB showed swollen mitochondria with fewer cristae and vacuolation of the matrix. Thus damage to mitochondria by EB provides structural evidence of inhibited mitochondrial protein synthesis. This study shows that EB by blocking mitochondrial protein synthesis inhibits the nuclear DNA synthesis and division of proliferating lymphocytes. These observations suggest that mitochondrial protein synthesis is crucial for cell proliferation (JPMA 32:114, 1982).