Fluoroquinolones (FQ) are broad-spectrum antibacterial agents widely used for the treatment of infections with various types of gram negative and gram positive bacteria. Specifically, gatifloxacin (GFX) is under development as a component in a new antituberculosis fixed-dose drug combination. In the context of this project, GFX was also tested for genotoxic activity in human peripheral lymphocytes, and the induction of chromosomal aberrations by GFX in PHA-M stimulated cultured human lymphocytes, investigated under conditions of conventional and increased expression times, was further compared to the analogous effects induced by some other second- and third-generation FQ antibacterial agents, namely ofloxacin (OFX), ciprofloxacin (CFX) and sparfloxacin (SFX). OFX did not induce any significant chromosomal aberrations in human lymphocytes. CFX and SFX exhibited slight to moderate clastogenic potential at cytotoxic concentrations (150, 175, 200 and 225 microg/ml), and GFX, a third-generation FQ, induced a clear, concentration-dependent increase in the frequency of chromosomal aberrations at cytotoxic concentrations (150, 200 and 250 microg/ml). These effects were not apparent when metaphases were analysed at the conventionally used sampling time of 24 h, but only after prolongation of the expression time between treatment and harvesting to a sampling time of 36 h (4 h exposure and 32 h expression period). Also, an increased incidence of numerical aberrations (polyploidy and endoreduplication) was seen with GFX at non-cytotoxic concentrations (12.5, 25, 50 and 75 microg/ml). These effects can be attributed to the slight cross-reactivity of FQs between their inhibitory activity towards their intended targets, the prokaryotic type II topoisomerase enzymes DNA gyrase and topoisomerase IV, and the analogous mammalian enzyme topoisomerase II. We have also observed the formation of polycentrics, i.e., chromosomes with five to six centromeres, a rarely reported structural aberration, in GFX-treated cells. The significance of these observations with respect to the conventional conduct of such studies and to the interpretation of the effects is discussed.
Strontium is a trace element that has no known essential biological role. The divalent cation, Sr 2+ , displays physicochemical properties similar to those of the abundant and biologically essential cations Ca 2+ and Mg 2+ . Abundant release of strontium is known to be the effect of radionuclide explosions. As there is no special strain for the removal of strontium from the effected environments, a strontium-resistant strain of Neurospora crassa (SRR) was obtained by repeated subculturing of the wild type on strontium containing agar medium. Neurospora crassa SRR was obtained by repeated subculturing, then the stability of the mutant was compared with wild type in terms of uptake, cellular partitioning and cross-resistant to other metals. Neurospora crassa SRR is twelve fold more resistant to strontium ions compared with the wild type. Resistance was stable on repeated subculturing of SRR on strontium-free media. Neurospora crassa SRR is also cross-resistant to calcium (fourfold). Higher concentrations of calcium ions are required to reverse growth inhibition due to strontium toxicity in Neurospora crassa SRR, compared with the wild type. The mechanism of strontium uptake is shown to be primarily due to binding of strontium to mycelia and cell walls. Efflux of mycelial strontium was also observed in wild type and strontium-resistant Neurospora crassa. The characteristics of SRR in comparison with wild type Neurospora crassa are discussed in relation to the mechanisms of strontium resistance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.