Ultrastructural correlates of the protection afforded by niacinamide against sulfur mustard-induced cytotoxicity of human lymphocytes in vitro.
Sulfur mustard (HD) has been shown to cause a concentration-dependent decrease in viability of human lymphocytes in vitro as measured by dye exclusion; this decrease is preventable by inhibitors of poly(adenosine diphosphatase ribose) polymerase such as niacinamide. The present study investigates the morphologic correlates of the protection afforded by niacinamide through scanning and transmission electron microscopic analysis of human lymphocytes incubated in the presence or absence of 10(3) M niacinamide for 24 h at 37 degrees C and exposed in vitro to 10(-3) M HD. Lymphocytes exposed to HD alone demonstrated 30% to 40% viability and 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. In the presence of niacinamide HD-treated lymphocytes had a viability of 87% and, except for blunting of the microvilli, essentially normal ultrastructure. Although the sequence of observed ultrastructural changes was not established, results of this morphologic study suggest that, in addition to the prevention of plasmalemmal defects and dye infusion, the mechanism of niacinamide protection appears to include preservation of the morphologic and functional integrity of cellular organelles.
Petrali
J P
JP
Comparative Pathology Branch, USAMRICD, Aberdeen, MD 21010.
Oglesby
S B
SB
Meier
H L
HL
D002462:Cell Membrane / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009150:Mustard Compounds / Q000494:pharmacology*; D009151:Mustard Gas / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D014617:Vacuoles / Q000648:ultrastructure
D002843:Chromatin; D009150:Mustard Compounds; D009536:Niacinamide; D009151:Mustard Gas