title: Interaction of drugs with extranuclear genetic elements and its consequences.
abstract: Bacterial ancestry of mitochondria and plastids is now generally accepted. Both organelles contain their own DNA and transcription-translation apparatus of a prokaryotic type. Due to this fact these systems carry bacteria-like properties. Thus organellar DNA and ribosomes are essentially different from nuclear DNA and cytoplasmic ribosomes in physical as well as in functional respects. Due to the bacterial character of both types of organelles they are susceptible to various antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit mitochondrial (plastidial) biogenesis. Therefore the cellular content of mitochondria (plastids)-made proteins decreases during cytoplasmic turnover or cell division in the presence of these drugs. Such drug activity consequently leads to a reduced capacity for oxidative phosphorylation or photosynthesis. Organellar genomes are less stable and more sensitive to mutagenesis as compared to nuclear genome. It means also that genotoxic agents induce various disorders of mitochondrial (plastidial) functions. Impairments in the respiratory chain are associated with structural as well as functional abnormalities of mitochondria. These are clinically expressed mostly in tissues with a high demand for ATP: brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively tumor cell proliferation. Therefore they may be considered for use in anticancer therapy. The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics. Various model organisms suitable for detection of xenobiotic effect on mitochondria (plastids) are presented as well as the possible consequences of such interaction.
authors.affiliation: Institute of Molecular and Subcellular Biology, Comenius University, Bratislava, Czechoslovakia.
authors.forename: L
authors.initials: L
authors.lastname: Ebringer
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D004247:DNA