Ultrastructural Correlates of the Protection Afforded by Niacinamide against Sulfur Mustard-Induced Cytotoxicity of Human Lymphocytes in Vitro

摘要

Previous work has shown that HD causes a concentration-dependent decrease in the viability of human lymphocytes as measured by dye exclusion. It was also shown that this decrease in viability was preventable by inhibitors of poly(ADP-ribose) polymerase, such as niacinamide. Present work concerns morphological correlates of the protection afforded by niacinamide through scanning and transmission electron microscopy study of human lymphocytes exposed to .001 M sulfur mustard (HD) incubated in the presence or absence of .001 M niacinamide for 24 hours at 37 C. Lymphocytes exposed to HD alone demonstrated 30%-40% viability and presented loss of microvilli, large cytoplasmic vacuoles, extensive blebbing of the perinuclear envelope, loss of cytoplasmic organelles, condensation of nuclear chromatin and multiple perforations of the plasmalemma. HD-treated lymphocytes in the presence of niacinamide had a viability of 87% and, except for blunting of microvilli, presented essentially normal ultrastructure. Although the sequence of the observed ultrastructural changes was not established, results of this morphologic study suggest that, in addition to the prevention of plasmalemma deficits and dye infusion, the mechanism of niacinamide protection appears to include the preservation of morphologic and functional integrity of cellular organelles. (AW)