RESUMEN
The largest metropolitan centers in northeastern region of Brazil are all located near the coast, and industrial, tourist, and agro-industrial activities are the principal causes of water contamination due to discharges of untreated sewage. Adverse environmental conditions can often be detected by analyzing the genetic material of organisms exposed to pollutants, and furnish an overview of environmental quality. We evaluated possible damage to the DNA of one of the fish resources most widely consumed and commercialized by coastal communities in northeastern Brazil, Mugil curema ("tainha"). Erythrocytes from M. curema were analyzed by the presence of micronuclei and by comet assay (single cell gel electrophoresis, SCGE). Statistical comparisons to both tests revealed considerably greater genomic damage in polluted estuaries than in the control site (pâ¯<â¯0.05), suggesting strong genotoxic impacts on the specimens evaluated, principally among those taken near localities with dense demographic and industrial development.
Asunto(s)
Ensayo Cometa , Daño del ADN , Smegmamorpha/genética , Animales , Brasil , Monitoreo del Ambiente , Eritrocitos/fisiología , Estuarios , Pruebas de Micronúcleos , UrbanizaciónRESUMEN
BACKGROUND: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line. METHODS: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay. RESULTS: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26µg/mL after 72h incubation. None of the compounds were cytotoxic to PBMC. After 48h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC. CONCLUSION: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells).