Brain neuronal chromatin responses in acute soman intoxicated rats.
Male Sprague-Dawley rats (200 g) were injected subcutaneously with soman, a potent neuronal acetylcholinesterase (AChE) inhibitor, at doses of 0.5, 0.8 and 1.0 LD50 (1 LD50 = 135 micrograms/kg) before decapitation at 1 and 24 h post-exposure. Correlative data were obtained on the severity of brain AChE inactivation and physicochemical changes in nuclear chromatin of cerebrocortical (layer V) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity; conversely, increases in F-DNA yield and chromophore area signify enhanced neuroexcitation. At 1 hr post-soman there was a dose-dependent inactivation of AChE with a moderate increase in chromatin activation, i.e., nuclear hypertrophy and chromatin dispersion. At 24 hr post-soman there was a partial restoration of AChE activity, notably in striatal neurons, with a suppression in chromatin template activity. These data indicate that actions of soman on neuronal functioning are time-dependent. The absence of any dose-related neuronal chromatin changes may signify existence of non-cholinergic mediated events.
D000110:Acetylcholinesterase / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; D003592:Cytophotometry; D004247:DNA / Q000378:metabolism; D008297:Male; D009562:Nissl Bodies / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012394:Rosaniline Dyes; D012999:Soman / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; C007722:Feulgen stain; D012394:Rosaniline Dyes; D004247:DNA; D012999:Soman; D000110:Acetylcholinesterase