DNA damage induced by methyl tertiary-butyl ether in vivo and in vitro

Abstract

To investigate the mechanism of methyl tertiary-butyl ether (MTBE)-induced animal carcinoma. Single cell gel electrophoresis assay (SCGE), DNA cross-links test and unscheduled DNA synthesis (UDS) assay were conducted with cultured rat type II pneumocytes and rat hepatocytes in vitro. Except UDS assay, the same experiment was performed in hepatocytes, renal cells and pneumocytes of mice administrated MTBE by inhalation at 0, 108, 1,440 and 4,968 mg/m(3) for 20 consecutive days. Simultaneously, the contents of malondialdehyde (MDA) in homogenates of lung and kidney were determined. The lengths of DNA migration in mice hepatocytes at 1,440, 4,968 mg/m(3) of MTBE, renal cells at all doses of MTBE, and pneumocytes at 4,968 mg/m(3) were greater than those in negative controls. There was dose-effect relationship between the concentration of MTBE and hepatocytes DNA migration lengths in mice (r = 0.997, P = 0.003). MTBE of 1,440 and 4,968 mg/m(3) contributed to a rise in MDA of renal homogenates in female mice (P < 0.05). MTBE above 0.050 mmol/L caused greater DNA migration in cultured rat type II pneumocytes and rat hepatocytes in vitro (P < 0.05), and also with dose-effect relationship (r(lung) = 0.967, r(liver) = 0.963, P < 0.05)). In UDS assay, DNA synthesis of rat type II pneumocytes and rat hepatocytes were increased at the concentration of 5.0 mmol/L and 10.0 mmol/L of MTBE. MTBE has some genotoxicity on DNA, and the single strand breaks of cell and lipid peroxidation may be one of the possible mechanism of MTBE-induced hepatic and renal tumors of animal.