Multicolor FISH using tándem probes to detect Chromosome alterations in humans cells and populations exposed to genotoxic agents

12 páginas, 2 figuras y 2 tablas estadísticasFluorescence in situ hybridization (FISH) with chromosome- or region-specific DNA probes is being increasingly used in cytogenetic studies to detect aneuploidy in interphase human cells. This technique utilizes chemically modified DNA sequences (probes) which hybridize to distinct regions, often blocks of repetitive DNA, located on specific chromosomes. Hybridization with these probes in situ results in the staining of a compact chromosomal región which can be easily detected on metaphase chromosomes or within interphase nuclei. The number of chromosomes within a given cell is then determined by counting the number of hybridized regions. Where conventional cytogenetics is limited to actively proliferating cells or those which could be stimulated to divide in vitro such as peripheral blood lymphocytes, FISH studies with centromeric probes can be conducted on interphase cells, significantly increasing the types of cells and tissues available for analysis.Peer reviewe

Discovery and Optimization of Benzotriazine Di-<i>N</i>-Oxides Targeting Replicating and Nonreplicating Mycobacterium tuberculosis

Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-<i>N</i>-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (<b>20q</b>) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC₅₀) against Vero cells of 25 μg/mL. <b>20q</b> also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. <b>20q</b> was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs