Antibacterial drugs and their interference with the biogenesis of mitochondria in animal and human cells.
Mitochondrial RNA and protein synthesis in mammalian cells is sensitive to inhibition by a variety of antibiotics which are used in medical practice. In spite of the intrinsic sensitivity of the synthetic processes to these drugs it appears that inhibition in intact cells and living organisms is not observed in all cases because the cellular membranes may act as barriers which prevent the antibiotics from reaching their intramitochondrial targets. This holds for the rifamycins, the lincomycins and a number of macrolides, but not for chloramphenicol and its analogues. Some of the toxic side-effects of the latter antibiotics can be related to their antimitochondrial action. For the tetracyclines selectivity in permeability exists in the sense that some cell types are permeable and other are not. The hypothesis is developed that the deliberate inhibition of mitochondrial protein synthesis in vivo may lead to cell proliferation arrest and offer a device in combined modality treatments of malignant growths. This hypothesis is supported by the results of two studies with experimental tumour models in rats and by retrospective and prospective clinical data.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000187:drug effects; D013754:Tetracyclines / Q000494:pharmacology; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D013754:Tetracyclines