Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

“…In the epidermis a disorganization of basal cells associated with an increase in the number of pyknotic nuclei, which is concordant with the dose-dependent increase in apoptosis that we have recently observed in the same model (Batal et al, 2013), led to the formation of microvesications and the complete destruction of epidermis in a dose-dependent manner. In dermis, SM exposure induced an inflammatory response including edema, hemorrhage, activation of mast cells and recruitment of neutrophils associated with a dose-dependent transcriptional response of inflammatory mediators in skin lesion.…”

“…In view of our results, we can hypothesize that the same mechanism takes place in SM-induced epidermal response. Indeed the dosedependent increase of inflammatory mRNA mediators was associated with an increase in number of pycknotic keratinocytes typical of the apoptotic process that we have recently correlated to the dose-dependent increase of SM-induced DNA adducts in the same SKH-1 hairless mouse model (Batal et al, 2013). So, inflammatory mediators could be used as biological markers of severity of SM-induced skin lesions.…”

“…For this, access to animal models is absolutely mandatory. In the last years, the hairless mouse has become the model of choice for investigating the effects of SM or of its monofunctional analogue CEES (Batal et al, 2013;Clery-Barraud et al, 2012;Dorandeu et al, 2011,b;Jain et al, 2011a,b;Joseph et al, 2011;Tewari-Singh et al, 2009;Vallet et al, 2012). Emphasis was placed in many of these studies on the inflammatory skin response, either after liquid CEES exposure (Jain et al, 2011a,b;Tewari-Singh et al, 2009) or SM vapor exposure (Joseph et al, 2011;Vallet et al, 2012).…”

Sulfur and nitrogen mustards induce characteristic poly(ADP-ribosyl)ation responses in HaCaT keratinocytes with distinctive cellular consequences

“…In addition, bi functional mustards, such as SM, HN2, or chlorambucil form biadducts between two guanine N7 positions to yield bis(N7guanine ethyl) sulfide (N7 Gua ETE N7 Gua) DNA crosslinks. Quantitative analysis estimated the relative distribution of these adducts to be $60 88% dG monoadducts, $10 42 % dG crosslinks, and $1 10% dA monoadducts depending on the methods used, the target material/tissue exposed, and the dose applied (Batal et al, 2013;Fidder et al, 1994;Yue et al, 2014). Crosslinks can be detected as early as 30 min after exposure in human lymphocytes (Debiak et al, 2011) and persist in SM exposed mouse tissue for up to several weeks (Batal et al, 2013).…”

“…Quantitative analysis estimated the relative distribution of these adducts to be $60 88% dG monoadducts, $10 42 % dG crosslinks, and $1 10% dA monoadducts depending on the methods used, the target material/tissue exposed, and the dose applied (Batal et al, 2013;Fidder et al, 1994;Yue et al, 2014). Crosslinks can be detected as early as 30 min after exposure in human lymphocytes (Debiak et al, 2011) and persist in SM exposed mouse tissue for up to several weeks (Batal et al, 2013). Interestingly, after cutaneous exposure, SM induced DNA adducts could also be detected systemically in many internal organs, such as brain, lung, kidney, and spleen (Batal et al, 2014).…”