In vivo effects of intercalating and nonintercalating drugs on the tertiary structure of kinetoplast deoxyribonucleic acid.
The kinetoplast DNA (kDNA) of cultured Trypanosoma cruzi consists mostly in a large network of numerous minicircular molecules (approximately 25 000), with a very low degree of superhelicity. When the intercalating drugs ethidium bromide and 9-hydroxyellipticine were added to the growth medium in concentrations producing trypanocidal effects, the superhelicity of the kDNA was significantly increased. In contrast, the nonintercalating drug berenil had no effect on the superhelicity of kDNA. In the kDNA extracted from trypanosomes resistant to ethidium bromide or 9-hydroxyellipticine, those drugs induce similar effects, although to a lesser extent than in the wild strain.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004278:DNA, Superhelical / Q000378:metabolism*; D004351:Drug Resistance; D004611:Ellipticines / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D009690:Nucleic Acid Conformation; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*
D000470:Alkaloids; D004278:DNA, Superhelical; D004611:Ellipticines; D046911:Macromolecular Substances; D004247:DNA; C008009:9-hydroxyellipticine; D004996:Ethidium