Cytophotometric analysis of T-2 toxin induced alterations in chromatin condensation and neuronal nuclear volume of rat supraoptic-magnocellular neurons.

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.