Abstract
Testicular effects of chemical mixtures may differ from those of the individual chemical constituents. This study assessed the co-exposure effects of the model germ cell- and Sertoli cell-specific toxicants, X-irradiation (x-ray), and 2,5-hexanedione (HD), respectively. In high-dose studies, HD has been shown to attenuate x-ray-induced germ cell apoptosis. Adult rats were exposed to different levels of x-ray (0.5 Gy, 1 Gy, and 2 Gy) or HD (0.33%), either alone or in combination. To assess cell type-specific attenuation of x-ray effects with HD co-exposure, we used laser capture microdissection (LCM) to enrich the targeted cell population and examine a panel of apoptosis-related transcripts using PCR arrays. The apoptosis PCR arrays identified significant dose-dependent treatment effects on several genes, with downregulation of death receptor 5 (DR5), Naip2, Sphk2, Casp7, Aven, Birc3, and upregulation of Fas. The greatest difference in transcript response to exposure was seen with 0.5 Gy x-ray exposure, and the attenuation effect seen with the combined high-dose x-ray and HD did not persist into the low-dose range. Examination of protein levels in staged tubules revealed a significant upregulation in DR5, following high-dose co-exposure. These results provide insight into the testis cell-specific apoptotic response to low-dose co-exposures of model testicular toxicants.
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