RESUMO
OBJECTIVE: The aim of this study was to ascertain whether genetic polymorphism affects susceptibility of individuals to nephrotoxic potentials of benzene, toluene, ethyl-benzene, and xylenes (BTEXs). METHODS: Fifty BTEXs exposed workers with one or more abnormal parameter of kidney function and 232 referent subjects, with similar exposure history, free from any abnormal kidney parameters were investigated. Atmospheric concentrations of BTEXs were measured. In addition, genetic polymorphisms were determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). RESULTS: The frequencies of GSTP1âIle-Val/Val-Val, null GSTT1, and null GSTT1/GSTM1 genotypes and mean values of blood urea nitrogen and plasma creatinine were significantly higher, while average glomerular filtration rate was significantly lower in cases than in referent subjects. CONCLUSION: These findings indicate that individuals carrying null GSTT1 or null GSTT1/GSTM1 are more susceptible to nephrotoxic properties of BTEXs compounds.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Derivados de Benzeno/toxicidade , Citocromo P-450 CYP2E1/genética , Predisposição Genética para Doença , Nefropatias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/metabolismo , Benzeno/metabolismo , Benzeno/toxicidade , Derivados de Benzeno/metabolismo , Nitrogênio da Ureia Sanguínea , Indústria Química , Creatinina/sangue , Estudos Transversais , Genótipo , Taxa de Filtração Glomerular , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Nefropatias/fisiopatologia , Masculino , Polimorfismo de Fragmento de Restrição , Tolueno/metabolismo , Tolueno/toxicidade , Xilenos/metabolismo , Xilenos/toxicidadeRESUMO
Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.