Ballough G P, Pritchard G A, Miller-Patrick K, Kan R K, Anthony A
Biology Department, Pennsylvania State University, University Park 16802.
Life Sci. 1989;45(2):189-96. doi: 10.1016/0024-3205(89)90294-4.
Quantitative cytophotometry and ocular filar micrometry were used to monitor T-2 toxin induced alterations in chromatin and neuronal nuclear volume in supraoptic-magnocellular neurons of rat hypo-thalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.0 and 1.5 X LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify changes in the susceptibility of chromatin to Feulgen acid hydrolysis. Changes in neuronal nuclear volumes were also determined histometrically. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in F-DNA reactivity were observed in the 0.5, 0.75, and 1.0 X LD50 groups (i.e. 3.7%, 4.4% and 2.5%, respectively); however, rats receiving 1.5 X LD50 T-2 toxin showed no difference in F-DNA reactivity compared to controls. In addition, ocular filar micrometry demonstrated increased neuronal nuclear volumes in all groups receiving T-2 toxin, and following an inverse trend to that seen with F-DNA stainability. Additional observations included pronounced polydipsia, polyphagia and horripilation in the experimental groups, independent of the dosages employed; these changes were evident within 1 hour post-injection. It is postulated that the T-2 toxin induced reduction in the susceptibility of chromatin to Feulgen acid hydrolysis and concomitant increases in neuronal nuclear volumes represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is evident that an impaired ability to osmoregulate is among the earliest indications of acute T-2 toxin mycotoxicosis.
采用定量细胞光度法和眼丝测微法，监测T-2毒素诱导的大鼠下丘脑视上核大细胞神经元染色质和神经元核体积的变化。给30只雄性Sprague-Dawley大鼠（200-220g）腹腔注射一次T-2毒素（0.5、0.75、1.0和1.5倍半数致死剂量），这是一种单端孢霉烯族霉菌毒素；给药8小时后将大鼠断头。对脑切片进行化学计量的福尔根DNA染色后，采用扫描积分显微密度测定法量化染色质对福尔根酸水解敏感性的变化。还通过组织测量法确定神经元核体积的变化。在视上核的大细胞神经元中，0.5、0.75和1.0倍半数致死剂量组的F-DNA反应性显著降低（分别为3.7%、4.4%和2.5%）；然而，接受1.5倍半数致死剂量T-2毒素的大鼠与对照组相比，F-DNA反应性没有差异。此外，眼丝测微法显示，所有接受T-2毒素的组中神经元核体积均增加，且与F-DNA染色性呈相反趋势。其他观察结果包括，各实验组均出现明显的烦渴、多食和竖毛现象，与所用剂量无关；这些变化在注射后1小时内就很明显。据推测，T-2毒素诱导的染色质对福尔根酸水解敏感性降低以及神经元核体积的相应增加，是代谢活性受损的早期迹象。由于这些神经元是血管加压素（抗利尿激素）合成的重要部位，这些数据表明渗透压调节能力受损。中毒后不久出现明显的烦渴是这种损害的进一步证据。尽管这些发现没有提供与渗透压调节破坏机制相关的见解，但很明显渗透压调节能力受损是急性T-2毒素霉菌毒素中毒最早的迹象之一。
