ABSTRACT
Objective To investigate the toxic effects and mechanisms of sulphur mustard on DNA damage of human immortalized epidermal keratinocytes (HacaT cells).Methods The inhibitory effect of sulphur mustard on the proliferation of HacaT cells was detected by CCK-8 method.The apoptosis index of cells was measured by Annexin V-FITC method.The effects of sulphur mustard on DNA damage were detected by single cell gel electrophoresis.The expression levels of DNA damage and repair related proteins were detected by Western blot.Results The proliferation rate of HacaT cells was inhibited in a dose-dependent manner after treatment with sulphur mustard for 24 h (IC50 value was 121 mol/L).The apoptotic and comet tailing rates of cells treated with sulphur mustard also increased in a dose-dependent manner.The expression levels of DNA damage and repair related proteins were changed after treatment with sulphur mustard.Conclusion Sulphur mustard has significant cytotoxic effect on HacaT cells,and can induce apoptosis and DNA damage.In addition,ATM-P53-γH2AX-PARP signaling pathway plays an important role in the repair of DNA damage induced by sulphur mustard.
ABSTRACT
Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver, skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.
ABSTRACT
Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.
ABSTRACT
In this study, we observed the efTects of systemic poisoning by sulphur mustard (SM) on DNA biosynthesis of internal organs and protective action of antidotes in mice.The results showed that the systemic poisoning by SM produced a strong depression of [3H]-TdR incorporation into DNA biosynthesis, which was characterized by rapidity, severity and rapid recovery.It is suggested that mammal an organism has a marked physiological compensation, regeneration and repair activity for DNA damage.Antidote sodium thiosufate alone or in combination with unithiol (DMPS) has satisfactory protective effects on depression of DNA biosynthesis in mice poisoned by SM.