Ethylbenzene is an important industrial chemical that has recently been classified as a possible human
carcinogen (International Agency of Research on
Cancer class 2B), but the available data do not support the genotoxic mechanism of
ethylbenzene-induced
tumors in kidney. We investigated the effects of
ethylbenzene on renal ultrastructure and explored the nongenotoxic mechanism of mitochondria-mediated apoptosis pathway. Forty male Sprague-Dawley rats were used as a vivo model with
ethylbenzene inhalation for 13 weeks, and the metabolites of
ethylbenzene,
mandelic acid (MA), and
phenylglyoxylic acid (
PGA) in urine were examined by high-performance liquid chromatography. Meanwhile, the ultrastructure of renal tubular epithelial cells was observed, and cell apoptosis was detected via
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Furthermore, we investigated the expression levels of
messenger RNA (
mRNA) and
protein of bax, bcl-2,
cytochrome c,
caspase-9, and
caspase-3 in rat kidney. With respect to levels of MA,
PGA, and MA +
PGA, a significant dose-dependent increase was observed in 4335 and 6500 mg/m(3)
ethylbenzene-treated groups against the control group. The mitochondria of renal tubular epithelial cells became a compact and vacuolar structure in 6500 mg/m(3)
ethylbenzene-treated group, and
ethylbenzene induced a significant increase in the number of apoptotic cells as compared to the control group. In addition, enhanced
mRNA and
protein expression levels of all measured genes were observed in various
ethylbenzene-treated groups except the decreased bcl-2 expression levels. Our results indicated that
ethylbenzene may induce apoptosis of renal tubular epithelial cells via mitochondria-mediated apoptotic pathways. MA and
PGA in urine might be a parameter of
biological dose in vivo after
ethylbenzene inhalation.