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      Teratogenic Effects of Sulfur Mustard on Mice Fetuses

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          Abstract

          Introduction

          Sulfur Mustard (SM) has been used as a chemical warfare agent, in the World War I and more recently during Iraq-Iran war in early 1980s’. Its biological poisoning effect could be local or systemic and its effect depends on environmental conditions, exposed organs, and the extent and duration of exposure. It is considered as a strong alkylating agent with known mutagenic, carcinogenic effects; although a few studies have been performed on its teratogenicity so far.

          Materials and Methods

          Mice were administered with SM intraperitoneally with a dose of 0.75 and 1.5 mg/kg in different periods of their gestation (gestational age of 11, 13 and 14 weeks). Control mice groups were included. Between 5 and 9 mice were used in each group. Dams underwent cesarean section on day 19 of their gestation. External examination was performed on the animals investigating craniofacial and septal defects and limb malformations such as adactyly and syndactyly. All data were analyzed by Chi-Square test and Fisher's exact test. The P- value less than 0.05 was considered significant.

          Results

          Craniofacial and septal defects as well as the limb malformations were the most common types of birth defects, displaying an extremely complex biomedical problem.

          Conclusion

          This study confirms a significant correlation between SM exposure and its teratogenic effect. We postulated that the malformations could be caused by an uncontrolled migration of neural crest cells, causing developmental disorders. In addition to environmental factors, modifying genes could play an important role in the pathogenesis of the defects.

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          Most cited references29

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          Gene/environment causes of cleft lip and/or palate.

          J Murray (2002)
          Craniofacial anomalies, and in particular cleft lip and palate, are major human birth defects with a worldwide frequency of 1 in 700 and substantial clinical impact. A wide range of studies in developmental biology has contributed to a better knowledge of how both genes and environmental exposures impact head organogenesis. Specific causes have now been identified for some forms of cleft lip and palate, and we are at the beginning of a time in which the common nonsyndromic forms may also have specific etiologies identified. Mouse models have an especially important role in disclosing cleft etiologies and providing models for environmental cotriggers or interventions. An overview of the gene-environment contributions to nonsyndromic forms of clefting and their implications for developmental biology and clinical counseling is presented.
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            Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review.

            A review of the literature pertaining to the incidence of cleft lip, cleft palate, and cleft lip and palate in different races is presented. The studies have been evaluated according to the method used to record the incidence rate. Half of the studies include in their base population livebirths, stillbirths, and abortions, or livebirths and stillbirths to record the incidence rate. In addition, in most of the studies, clefts with associated malformations and possible syndromes are included in the reported incidence. There is evidence, however, to suggest that the risk of developing clefts in stillbirths and abortions is three times as frequent as in livebirths and that clefts with associated malformations behave differently epidemiologically from clefts without associated malformations. It is suggested, therefore, that the incidence of cleft lip, cleft palate, and cleft lip and palate should be studied separately for each group, namely for livebirths, stillbirths, and abortions and should be reported separately for clefts without associated malformations, clefts with associated malformations, and syndromes. More research is needed to study the risk of developing clefts among the various groups that exhibit different epidemiologic behavior for each race.
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              Comparison of early and late toxic effects of sulfur mustard in Iranian veterans.

              Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We compare these effects based on the experience in Iranian veterans exposed to the agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness, lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin lesions varied from erythema to bullous necrotization. Initial leukocytosis and lymphopenia returned to normal within four weeks in recovered patients, but marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main respiratory complications were chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen of the severely intoxicated patients were diagnosed with delayed keratitis, having corneal vascularization, thinning, and epithelial defect. Respiratory complications exacerbated over time, while cutaneous and ocular lesions decreased or remained constant. Both the severity and frequency of bronchiectatic lesions increased during long-term follow-up. The only deteriorating cutaneous complication was dry skin. The maximum incidence of delayed kaeratitis was observed 15 to 20 years after initial exposure. Being suggested as the main cause ofassociated with malignancies and recurrent infections, natural killer cells were significantly lower 16 to 20 years after intoxication.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                IJBMS
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                May-Jun 2012
                : 15
                : 3
                : 853-859
                Affiliations
                [1 ] Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ] Department of Basic Sciences, Mashhad Azad University, Mashhad, Iran
                Author notes
                [* ]Corresponding author: Tel: +98-511-8002245; Fax: +98-511-8002247; email: nazarabadim@mums.ac.ir
                Article
                IJBMS-15-853
                3586898
                23493485
                18fc98b4-a64a-404c-8196-3ad04a0ad20f
                © 2012: Iranian Journal of Basic Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 November 2011
                : 6 March 2012
                Categories
                Original Article

                malformation,sulfur mustard,teratogenicity
                malformation, sulfur mustard, teratogenicity

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