School of Pharmaceutical Science, Ohu University, Fukushima, Japan.
J Toxicol Sci. 2013;38(2):245-54. doi: 10.2131/jts.38.245.
Several studies have shown effects of diesel exhaust (DE) on the central nervous system, but the mechanism is unclear. Fetal mice were exposed to whole DE (contains gases and particles) in an inhalation chamber, and cerebrum gene expression changes were examined by gene assay (microarray and quantitative real-time PCR). By microarray, upregulation of Xist, B-raf and Drwms2 were detected. Especially, mRNA expression of Xist was increased in a concentration-dependent manner in male and female mice. Xist (X-inactive specific transcript) is a major effector of the X-inactivation process, and X-linked genes are highly expressed in brain tissue and consistent with a role in brain developments. By quantitative real-time PCR, Tsix (crucial noncoding antisense partner of Xist) and other X-linked genes (Mecp2, Hprt1, and Sts) were examined; Tsix was upregulated, and other X-linked genes were unaffected in the male and female mice. Our findings suggest that exposure to DE increases Xist and Tsix gene expression in utero without influencing X-linked gene expression. An examination of Xist gene expression changes may provide an important biomarker for DE-induced effects. The possibility of avoiding X-chromosome inactivation (XCI) mechanisms by minimizing exposure to DE is expected.
已有多项研究表明，柴油机废气（diesel exhaust，DE）会对中枢神经系统产生影响，但具体机制尚不清楚。本研究将胎鼠置于吸入式染毒舱中，使其暴露于全柴油机废气（包含气体和颗粒）中，通过基因检测（微阵列和实时定量 PCR）检测大脑基因表达的变化。微阵列结果显示，Xist、B-raf 和 Drwms2 的表达上调。特别是，Xist 的 mRNA 表达在雄性和雌性小鼠中均呈浓度依赖性增加。Xist（X 失活特异性转录本）是 X 染色体失活过程的主要效应因子，X 连锁基因在脑组织中高度表达，与脑发育有关。实时定量 PCR 结果显示，Tsix（Xist 的关键非编码反义伴侣）和其他 X 连锁基因（Mecp2、Hprt1 和 Sts）的表达也发生了变化；雄性和雌性小鼠的 Tsix 表达上调，而其他 X 连锁基因不受影响。这些发现提示，DE 暴露可增加宫内胎儿 Xist 和 Tsix 基因的表达，但不影响 X 连锁基因的表达。检测 Xist 基因表达的变化可能为 DE 诱导效应提供一个重要的生物标志物。通过减少 DE 暴露，有望避免 X 染色体失活（X-chromosome inactivation，XCI）机制。
