On the effect of inhibitors of mitochondrial macromolecular-synthesizing systems and respiration on the growth of cultured chick embryo cells.

Abstract

We have found that chick embryo fibroblasts (DEF) cultivated in the presence of tryptose phosphate broth (TPB) are inherently resistant to the growth inhibitory effect of ethidium bromide (EB). As demonstrated by cytochrome oxidase activity and oxygen consumption measurements, analyses of reduced-minus-oxidized cytochrome spectra and electron microscopic observations, TPB did not seem to prevent the inhibitory effect of EB on mitochondrial DNA transcription. EB-treated chick cell populations cultivated in the presence of TPB behave essentially the same as populations treated with chloramphenicol (CAM) and grow with mitochondria devoid of a functional respiratory chain. In contrast to CAM-treated CEF populations, however, the respiratory activity of EB-treated cell populations did not reappear when the cells were shifted back to EB-free medium. Attempts to demonstrate that TPB confers resistance to the growth inhibitory effect of carbomycin and mikamycin, inhibitors of the mitochondrial protein-synthesizing system, have failed, the drugs being cytotoxic at doses where protein synthesis on mitoribosomes is not suppressed. On the other hand, the present results demonstrated that chick cell populations proliferate in the presence of the respiratory inhibitors rotenone, antimycin A, amytal and oligomycin whether or not TPB is present in the growth medium.