A Vapor Exposure Model for Neonatal Mice

Published on Jan 1, 2002in Toxicology Mechanisms and Methods2.295
· DOI :10.1080/15376510209167936
Dana R. Anderson25
Estimated H-index: 25
(United States Army Medical Research Institute of Chemical Defense),
Larry W. Mitcheltree4
Estimated H-index: 4
(United States Army Medical Research Institute of Chemical Defense)
+ 3 AuthorsMark B. Gold4
Estimated H-index: 4
(United States Army Medical Research Institute of Chemical Defense)
Sources
Abstract
Sulfur mustard (HD) is a vesicant compound that was first used as a chemical warfare agent in World War I. (Papirmeister et al. 1991). Numerous animal models have been used to study HD-induced vesication. In this article, we describe modifications of the vapor cup model of Mershon and colleagues (1990) to establish a new vapor cup model for use in neonatal mice. The need to develop this model resulted from the development of gene-targeted knockout mice that can be used to evaluate the function of specific genes and their contribution to HD-induced pathology. However, the knockouts are haired mice; therefore, it is necessary to perform vapor exposures on the pups prior to their growing hair. Neonatal mice were anesthetized with isofluorane inhalation and placed in sternal recumbency on a 37°C isothermal pad to maintain body heat during exposure. The vapor cup consisted of a 1.5-mL microfuge tube cap (8 mm inside diameter) modified using a Dremel tool to contour its rim to better fit the curve of a mouse pu...
References20
Newest
#1Robert P. Chilcott (Defence Evaluation and Research Agency)H-Index: 23
#2R.F.R. Brown (Defence Evaluation and Research Agency)H-Index: 9
Last. P Rice (Defence Evaluation and Research Agency)H-Index: 2
view all 3 authors...
The severity and progression of skin lesions resulting from exposure to the chemical warfare agents Lewisite (L) and sulphur mustard (SM) have been investigated using the non-invasive biophysical methods of evaporimetry and reflectance spectroscopy in large white pigs in vivo. Erythema (redness) expressed immediately after exposure to L or SM vapours appeared to be related to the lesion severity as demonstrated by histopathological analysis. Skin brightness correlated well with scab formation wh...
32 CitationsSource
#1Thomas H. Snider (Battelle Memorial Institute)H-Index: 6
#2M. C. Matthews (Battelle Memorial Institute)H-Index: 2
Last. E. H. BraueH-Index: 1
view all 3 authors...
: Sulfur mustard (HD; 2,2'-dichlorodiethyl sulfide) can produce incapacitating blisters in humans following dermal exposure. Most non-human animal models, however, do not form the large fluid-filled blisters observed in humans. Many models, nevertheless, do produce similar damage at the dermal/epidermal junction when evaluated by histopathology. In this study, it was observed that the hairless guinea pig (HGP) exhibits similar histopathological responses following exposure to HD vapor. Two sets ...
10 CitationsSource
#1Ruowen Ge (NUS: National University of Singapore)H-Index: 32
Genetically manipulated animals generated by transgenic and gene-targeting (knockout) technology have contributed tremendously to our understanding of gene function and regulation at the molecular level in the context of the whole organism. They are also becoming powerful tools for human disease studies and therapeutic drug development. An overview of the current development of these animals and their application in biological and medical researches is provided in this article. Ann Acad Med Sing...
3 Citations
#1Thomas P. Logan (United States Army Medical Research Institute of Chemical Defense)H-Index: 2
#1Thomas P. Logan (United States Army Medical Research Institute of Chemical Defense)H-Index: 6
Last. Rodolfo Bongiovanni (United States Army Medical Research Institute of Chemical Defense)H-Index: 2
view all 6 authors...
ABSTRACTThe hairless guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD), bis(2-chloroethylsulfide), exposure. We determined the HD content in the skin of HGP after a 7-min exposure to vapors saturated with a mixture of HD and l4C-HD. Concentration/time (CT) values in the range of 2 μg/cm2/min were determined by counting skin 14C disintegrations per min (dpm) in animals euthanized immediately after exposure. These values are similar to human pe...
14 CitationsSource
#1A. Eldad (HUJI: Hebrew University of Jerusalem)H-Index: 8
#2Patrik Ben Meir (HUJI: Hebrew University of Jerusalem)H-Index: 1
Last. Hannah Ben-Bassat (HUJI: Hebrew University of Jerusalem)H-Index: 26
view all 6 authors...
Abstract Mustard gas (MS) has been used in chemical warface since World War I. The blistering skin lesions are slow to heal. Secondary inflammation might occur, as well as damage to organs distant from the original wound. Presently there is no specific antidote for burns and poisoning by MS. This study examined treatment modalities with free oxygen radical scavengers, copper-zinc, and manganese superoxide dismutase (SOD), for MS skin burns in an experimental guinea pig model. Each of the SOD com...
31 CitationsSource
#1P.J. Danneman (UTHSC: University of Tennessee Health Science Center)H-Index: 1
#2T.D. MandrellH-Index: 1
Although neonatal altricial rodents are frequently used in experimental projects in which they must undergo survival surgical procedures, there are few published guidelines for anesthetizing them. Many of the drugs and methods that are commonly used to anesthetize newborn rodents provide inadequate anesthesia or are associated with problems, such as excessively high mortality. A two-part study was undertaken with the intention of identifying agents or methods that can be used to provide humane, ...
104 Citations
#1A. ZlotogorskiH-Index: 1
#2M. GoldenhershH-Index: 1
Last. A. Shafran (HUJI: Hebrew University of Jerusalem)H-Index: 1
view all 3 authors...
Abstract The search for treatment and protection against the vesicant and inflammatory skin lesions induced by sulfur mustard suffers from the lack of a good in vivo reproducible model. We applied sulfur mustard (25–500 μg/cm 2 ) to the outer surface of the ears of 10 rabbits and measured the edema formation 12, 24 and 48 h post-application with a caliper especially designed for soft matter. There was a dose-dependent linear increase in edema magnitude in the range from 25 to 150 μg/cm 2 . Maxim...
16 CitationsSource
#1Kathleen J. Smith (United States Army Medical Research Institute of Chemical Defense)H-Index: 2
#2Robert P. Casillas (United States Army Medical Research Institute of Chemical Defense)H-Index: 20
Last. Brennie E. Hackley (United States Army Medical Research Institute of Chemical Defense)H-Index: 3
view all 6 authors...
Abstract In an effort to understand the pathophysiology of sulfur mustard (2,2′ dichlorodiethyl sulfide, HD)-induced cutaneous lesions, a number of animal models have been used. Animal models have been and will continue to be used in the development of therapeutic strategies to protect against and/or moderate lesions, and to potentiate wound healing after HD exposure. Upon reviewing the histopathologic features seen after HD-exposure, we propose roles for different animal models in HD-research. ...
81 CitationsSource
#1Carmen M. ArroyoH-Index: 1
Last. C. A. BroomfieldH-Index: 1
view all 3 authors...
5 Citations
#1Sally K. WixsonH-Index: 1
#2Kathleen L. SmilerH-Index: 1
Publisher Summary This chapter presents a comprehensive review of the literature regarding methods to provide anesthesia as well as analgesia to laboratory rodents. It focuses primarily on the predominant rodent species used in research, that is, mice and rats. Rodents require appropriate preoperative evaluation and care when planning experimental manipulations that require anesthesia. Colony history should be carefully reviewed to determine the source and health status of the animals. The age o...
92 CitationsSource
Cited By4
Newest
#1Gabriella M. Composto (RU: Rutgers University)H-Index: 5
#2Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
Last. Diane E. Heck (NYMC: New York Medical College)H-Index: 38
view all 8 authors...
Abstract Nitrogen mustard (NM) is a bifunctional alkylating agent that is highly reactive in the skin causing extensive tissue damage and blistering. In the present studies, a modified cutaneous murine patch model was developed to characterize NM-induced injury and to evaluate the efficacy of an indomethacin pro-drug in mitigating toxicity. NM (20 μmol) or vehicle control was applied onto 6 mm glass microfiber filters affixed to the shaved dorsal skin of CD-1 mice for 6 min. This resulted in abs...
10 CitationsSource
#1Thomas H. Snider (Battelle Memorial Institute)H-Index: 6
#2Mark R. Perry (Battelle Memorial Institute)H-Index: 4
Last. John S. GrahamH-Index: 18
view all 7 authors...
AbstractContext: Assessing the hazards of accidental exposure to toxic industrial chemical (TIC) vapors and evaluating therapeutic compounds or treatment regimens require the development of appropriate animal models.Objective: The objective of this project was to develop an exposure system for delivering controlled vapor concentrations of TICs to the skin of anesthetized weanling pigs. Injury levels targeted for study were superficial dermal (SD) and deep dermal (DD) skin lesions as defined hist...
3 CitationsSource
#1Li Xia (SJTU: Shanghai Jiao Tong University)H-Index: 8
#2Shankai Yin (SJTU: Shanghai Jiao Tong University)H-Index: 25
Last. Jian Wang (Dal: Dalhousie University)H-Index: 59
view all 3 authors...
Local gene transfection is a promising technique for the prevention and/or correction of inner ear diseases, particularly those resulting from genetic defects. Adeno-associated virus (AAV) is an ideal viral vector for inner ear gene transfection because of its safety, stability, long-lasting expression, and its high tropism for many different cell types. Recently, a new generation of AAV vectors with a tyrosine mutation (mut-AAV) has demonstrated significant improvement in transfection efficienc...
26 CitationsSource
#1Laurie B. Joseph (RU: Rutgers University)H-Index: 12
#2Donald R. Gerecke (RU: Rutgers University)H-Index: 18
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 10 authors...
Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1–14 days later. After 1 da...
47 CitationsSource