Changes in connective tissue macromolecular components of Yucatan mini-pig skin following application of sulphur mustard vapour

Lindsay, Christopher D.; Rice, Paul

doi:10.1177/096032719501400404

Cited by 29 publications

(12 citation statements)

References 26 publications

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“…Only laminin appeared to be degraded almost completely following exposure of skin to Lewisite, as indicated by the much reduced level of laminin antigen staining on the blots, although a small amount of laminin antigen was resolved between 45 and 66 kDa. This contrasts markedly with Lindsay and Rice (1995) in a study of the effects of sulphur mustard exposure in Yucatan mini-pigs, in which case sulphur mustard only induced a partial cleavage of laminin and had no effect on type IV collagen integrity.…”

Section: Discussioncontrasting

confidence: 84%

“…The fact that damage was found to both of these critically important basement membrane components, and to laminin in particular, following percutaneous Lewisite exposure of large white pigs strongly suggests that the potency of this vesicant may be attributable to its effects on these essential macromolecules that mediate dermo-epidermal attachment processes. The effects of Lewisite on laminin and type IV collagen observed in the present study are more severe than those found in a previous study on sulphur mustard effects in pigs (Lindsay and Rice, 1995), suggesting that there are important differences in the mechanism of action of both vesicants. That Lewisite should produce more severe effects on basement membrane macromolecules and yet generate more rapid healing of skin burns than sulphur mustard may be attributable to alkylation (by sulphur mustard) of the DNA and RNA of skin cell types, their metabolic processes and connective tissue components (Rice and Brown 1999;Naghii, 2002) that would normally be involved in skin regeneration and healing responses.…”

Section: Discussioncontrasting

confidence: 83%

“…The sections were rehydrated and stained for laminin and types III and IV collagen as described in Lindsay and Rice (1995). Photomicrographs were taken at a magnification of × 200.…”

Section: Preparation Of Skin For Immunostainingmentioning

confidence: 99%

“…Type III collagen was extracted using 0.5 M acetic acid. The following protocol describes the method used in the present study; it has been described previously in Lindsay and Rice (1995):…”

Section: Preparation Of Skin Extract Samples For Sds-pagementioning

confidence: 99%

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Examination of changes in connective tissue macromolecular components of large white pig skin following application of lewisite vapour

Lindsay

Hambrook

Brown

et al. 2004

J of Applied Toxicology

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The aim of this study was to provide information about the degradative processes that occur in major connective tissue components in skin following exposure of large white pigs to Lewisite vapour. Of particular interest were alterations in glycoproteins, which are known to mediate dermo-epidermal attachment (laminin and type IV collagen) and the main collagen found in the dermis (type III collagen). The immunostaining of transfer blots from skin extracts run on sodium dodecyl sulphate polyacrylamide gel electrophoresis gels revealed no evidence of cross-linking of laminin or of type III or IV collagen. However, there was evidence of a very considerable degradation of laminin and, to a lesser extent, of type IV collagen. Type III collagen did not appear to be degraded in skin exposed to Lewisite. These degradative processes appeared to be more severe than found in previous studies in Yucatan mini-pigs percutaneously exposed to sulphur mustard, in which only laminin was found to undergo partial cleavage rather than wholesale degradation. The results suggest that damage to macromolecular components in the sub-epidermal basement membrane in skin which mediate dermo-epidermal separation processes may be a common feature in the mechanism of action of vesicating agents such as Lewisite and sulphur mustard. It is of interest that the damage to laminin in this study appeared to be more severe than that previously found for sulphur mustard. This suggests that skin can suffer substantial damage yet, in the case of Lewisite exposure, recover relatively quickly. However, Lewisite is not an alkylating agent. Sulphur mustard, in contrast, generates characteristically slow healing lesions, most probably because of its ability to alkylate cell types that normally would be involved in skin regenerative processes.

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Section: Discussioncontrasting

confidence: 84%

Section: Discussioncontrasting

confidence: 83%

“…The sections were rehydrated and stained for laminin and types III and IV collagen as described in Lindsay and Rice (1995). Photomicrographs were taken at a magnification of × 200.…”

Section: Preparation Of Skin For Immunostainingmentioning

confidence: 99%

Section: Preparation Of Skin Extract Samples For Sds-pagementioning

confidence: 99%

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Examination of changes in connective tissue macromolecular components of large white pig skin following application of lewisite vapour

Lindsay

Hambrook

Brown

et al. 2004

J of Applied Toxicology

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“…To date a number of proteins have been shown to aggregate or breakdown on SM exposure, e.g. various keratins [7][8][9], and laminin [10,11]. There has been little research looking at the direct interaction of SM with cell membrane-associated proteins.…”

Section: Introductionmentioning

confidence: 99%

Direct binding of sulfur mustard and chloroethyl ethyl sulphide to human cell membrane-associated proteins; implications for sulfur mustard pathology

Sayer¹,

Whiting²,

Green³

et al. 2010

Journal of Chromatography B

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Toxicology of Chemical Warfare Agents

Maynard¹,

Chilcott²

2009

General, Applied and Systems Toxicology

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Irritant or toxic chemicals have been used in warfare since ancient times and a number of international laws have attempted to prevent the use of such weapons. However, chemical warfare agents remain to be a global threat and so it is important to maintain an understanding of their mechanism of action, their clinical effects and to identify effective treatment regimes. Chemical warfare agents have traditionally been classified according to their medical effect(s) or military application. Vesicant agents (for example, sulphur mustard and lewisite) are highly potent acute contact irritants and may cause severe skin damage following dermal exposure as well as extensive damage to other epithelial surfaces (such as the lungs and eyes). Vesicants are generally considered to be non‐lethal in that they cause debilitating (rather than fatal) injuries. Indeed, some chemicals are used specifically for their irritating (rather than lethal) effects. For example, the riot control agents CS and CR are potent lachrymators but generally lack any significant, systemic toxicity following respiratory or dermal exposure. In contrast, a number of chemicals have been specifically developed or used on account of their lethality and these include the nerve agents (such as sarin, tabun, soman and VX), lung damaging agents (phosgene and chlorine) and other systemic poisons such as cyanides. A large miscellany of other, more exotic chemicals exist and these include endogenous bioregulators as well as plant, animal, marine and fungal toxins.

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Changes in connective tissue macromolecular components of Yucatan mini-pig skin following application of sulphur mustard vapour

Cited by 29 publications

References 26 publications

Examination of changes in connective tissue macromolecular components of large white pig skin following application of lewisite vapour

Examination of changes in connective tissue macromolecular components of large white pig skin following application of lewisite vapour

Direct binding of sulfur mustard and chloroethyl ethyl sulphide to human cell membrane-associated proteins; implications for sulfur mustard pathology

Toxicology of Chemical Warfare Agents

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