Poly(ADP-ribose) polymerase inhibitors regulate the mechanism of sulfur mustard-initiated cell death in human lymphocytes.
Sulfur mustard (HD) produces slow-healing skin lesions that contain large, tight fluid-filled blisters. These lesions are the result of severe damage to areas of the body exposed to HD and require extensive medical care before complete recovery is achieved. Converting the mechanism of HD-initiated cell death from an inflammatory oncosis (homicide) to benign apoptosis (assisted suicide) may reduce the extent of cellular damage and the time required for healing. HD-exposed human lymphocytes lose cellular function, membrane integrity and viability, and suffer degradation of their nuclear components. The treatment of HD-exposed cells with poly(ADP-ribose) polymerase inhibitors prevents or alters the HD-initiated loss of cell viability, membrane integrity, cellular metabolic constituent (NAD) and cellular energy (ATP), while initiating alterations in nuclear constituents. It is hoped that by preventing or altering these HD-initiated changes we can limit the extent of the injury, decrease the time required for repair and reduce the loss of performance suffered by exposed individuals. The use of poly(ADP-ribose) polymerase inhibitors to assist in initiating apoptosis in affected cells should help to achieve these objectives while preventing the chance of further disease development later in the exposed individuals.
Meier
H L
HL
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA. Henry.Meier@ammed.apgea.army.mil
Millard
C
C
Moser
J
J
D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D003879:Dermatologic Agents / Q000633:toxicity*; D006801:Humans; D007249:Inflammation; D008214:Lymphocytes / Q000187:drug effects; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000032:analysis; D011041:Poisoning / Q000517:prevention & control; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology
D003879:Dermatologic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020011:Protective Agents; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D009151:Mustard Gas