RESUMO
(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC50 value of 5.68 µM, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 µM were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G1, G1/S, transition, and G2), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes.
Assuntos
Benzofenonas/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Mutagênicos/toxicidade , Adulto , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaio Cometa , Feminino , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Adulto JovemRESUMO
In recent years, the use of pesticides in agriculture has been steadily increasing, and associations between exposure to agricultural chemicals and DNA damage and cancer have been reported. Brazil is one of the world leaders in pesticide use; however, studies that evaluate the impact of pesticide exposure on cancer incidence and mortality are very scarce in the Brazilian population. The alkaline comet assay and the chromosome aberration (CA) test were used to evaluate primary DNA damage in the peripheral blood lymphocytes of workers exposed to a complex mixture of pesticides in two small rural communities in the municipalities of Tianguá and Ubajara, located in the western part of Ceará State (Northeast Brazil), which are among the largest agricultural areas of the state. The comet assay showed that the damage index and damage frequency observed in the exposed groups were significantly higher in relation to the controls (P < 0.05). On the other hand, no differences were detected regarding structural and numerical CAs in the communities evaluated. Additionally, the observed levels of DNA strand breaks and frequencies of CAs, stratified for exposure time, were not statistically different for individuals of either rural community. Our results suggest that the damages caused by pesticides in our study area were not great enough to induce permanent mutations or to interfere with mitotic apparatus formation; minimal pesticide damages could have undergone cellular repair, explaining the absence of structural and numerical CAs.