Toxicology Division, Institute of Environmental Toxicology, Ibaraki, Japan.
Immunopharmacol Immunotoxicol. 2011 Mar;33(1):193-200. doi: 10.3109/08923973.2010.495128. Epub 2010 Jun 23.
The thymus has long been known to be vulnerable to atrophy when exposed to variety of stimuli, including hormones, immunosuppressive pharmaceuticals, and environmental chemicals. The organochlorine pesticide methoxychlor (MXC) is an immunosuppressive agent thought to affect thymic atrophy by inducing apoptosis of thymocyte T cells. We sought to develop an experimental protocol to detect in vivo thymocyte apoptosis induced by MXC in Balb/c mice. We treated the mice with 150-400 mg/kg MXC. We then measured thymus weight, cell counts, caspase activity (3/7, 8, and 9), annexin V labeling of phosphatidylserine (PS) and DNA fragmentation. In MXC-treated mice we observed decreases in thymus weight and cell counts and increases in caspase activity (3/7, 8, and 9), annexin V PS labeling and DNA fragmentation. These results suggest that MXC induces thymic atrophy caused by thymocyte apoptosis, and that our protocol may be useful for detecting in vivo thymocyte apoptosis induced by environmental chemicals in short-time.
胸腺一直以来都容易受到各种刺激的萎缩,包括激素、免疫抑制剂和环境化学物质。有机氯农药甲氧滴滴涕(MXC)是一种免疫抑制剂,据认为通过诱导胸腺细胞 T 细胞凋亡而影响胸腺萎缩。我们试图开发一种实验方案,以检测 MXC 在 Balb/c 小鼠体内诱导的胸腺细胞凋亡。我们用 150-400mg/kg MXC 处理小鼠。然后,我们测量了胸腺的重量、细胞计数、半胱氨酸天冬氨酸蛋白酶(caspase)活性(3/7、8 和 9)、磷脂酰丝氨酸(PS)结合的 Annexin V 标记和 DNA 片段化。在 MXC 处理的小鼠中,我们观察到胸腺重量和细胞计数减少,caspase 活性(3/7、8 和 9)、 Annexin V PS 标记和 DNA 片段化增加。这些结果表明,MXC 诱导由胸腺细胞凋亡引起的胸腺萎缩,并且我们的方案可能有助于检测环境化学物质在短时间内诱导的体内胸腺细胞凋亡。