Effects of chloramphenicol on the physiology and fine structure ofTetrahymena pyriformis GL: Correlation between diminishing inner mitochondrial membrane and cell doubling

Summary

A time-dependent loss of tubular infolding of the inner mitochondrial membrane was reported recently as an effect of the cytostatic drug, methotrexate (MTX), onTetrahymena (Nilsson 1983); this finding was interpreted as an inhibition of mitochondrial protein synthesis. In the present study, the cells were exposed to chloramphenicol (CAP), an inhibitor of mitochondrial translation, at the same concentrations (1–25 mM) as MTX; the question asked was whether the two drugs acted similarly. CAP affected cell proliferation by causing a dose-dependent prolongation of the generation time, but at 10–25 mM permitted only a limited number of cell doublings, whereas 1 mM MTX inhibits growth after 5 cell doublings. With CAP the inner mitochondrial membrane diminished gradually in accordance with the number of cell doublings at 10–25 mM, but in 2 mM CAP, for example, some tubular infoldings were still present after 17 cell doublings. The gradual loss of the inner mitochondrial membrane correlated with a gradual decrease in the cellular ATP content, irrespective of the concentration of the drug but dependent on the progress of the cells through their first cycle when exposed to the drug; in cells which continued to proliferate, the ATP content remained at a value corresponding to 80% of the control value. With respect to cell proliferation, the two drugs act differently. CAP is less toxic than MTX, reflected in a 10 times shorter recovery time for cell proliferation after removal of CAP. Hence, although the structural manifestation of the action of the two drugs on mitochondria is identical, their target site may differ.