Accession Number : ADP008780


Title :   Sulfur Mustard-Induced Increase in Intracellular Calcium: A Mechanism of Mustard Toxicity


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Ray, R ; Majerus, B J ; Munavalli, G S ; Petrali, J P


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/p008780.pdf


Report Date : 13 May 1993


Pagination or Media Count : 11


Abstract : The effect of sulfur mustard (SM, bis-(2-chloroethyl) sulfide) on intracellular free Ca2+ concentration (Ca2+)i was studied in vitro using the clonal mouse neuroblastoma-rat glioma hybrid NG108-15 and primary normal human epidermal keratinocyte (NHEK) cell culture models. SM depletes cellular glutathione (GSH) and thus may inhibit GSH-dependent Ca2+-ATPase (Ca2+ pump), leading to a high (Ca2+) and consequent cellular toxicity. Following 0.3 mM SM exposure, GSH levels decreased 20-34% between 1-6 hr in NG108-15 cells. SM increased Ca2+)i, measured using the Ca2+-specific fluorescent probe Fluo-3 AM, in both NG108-15 cells (1030% between 2-6 hr) and NHEK (23-30% between 0.5-3 hr) . Depletion of cellular GSH by buthionine sulfoximine (1 mM), a specific GSH biosynthesis inhibitor, also increased (Ca2+, (88% at 1 hr) in NHEK, suggesting that GSH depletion may lead to increased Ca2+)i. Calcium, localized cytochemically with antimony, accumulated in increased amounts around mitochondria and endoplasmic reticula, in the cytosol, and in particular in the euchromatin regions of the nucleus beginning at 6 hr after 0.3 mM SM exposure of NG108-15 cells. Cell membrane integrity examined with the fluorescent membrane probe calcein AM was unaffected through 6 hr following 1 mM SM exposure; and cell viability (NG108-15 cells) measured by trypan blue exclusion was 80% of control through 9 hr following 0.3 mM SM exposure.


Descriptors :   *CALCIUM , *TOXICITY , *MUSTARD AGENTS , *CYTOCHEMISTRY , CONTROL , DEPLETION , PROBES , ACTIVATION , MEMBRANES(BIOLOGY) , DAMAGE , MODELS , RATS , HUMANS , REGIONS , VIABILITY , SULFUR , INHIBITORS , PUMPS , BLUE(COLOR) , CELLS(BIOLOGY) , VISCOSITY , ANTIMONY , SULFIDES , CULTURES(BIOLOGY) , BIOSYNTHESIS , ACIDS , EPIDERMIS , PEPTIDE HYDROLASES , GLUTATHIONE , ADENOSINE PHOSPHATES , MITOCHONDRIA , NEUROBLASTOMA


Subject Categories : Biochemistry
      Toxicology
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE