Alkylating agents such as sulfur mustard (S-Lost, mustard gas, SM, HD, bis(2- chloroethyl)sulfide, Yperite), predominantly used by military forces, and related chemotherapeutic drugs, e.g. chlorambucil (Cbl, trade name: Leukeran), are known to cause severe cellular damage without being fully understood on a molecular level. The discovery of sulfur mustard and its use as a chemical weapon was followed by the detection of associated, medically useful toxicological properties, which paved the way

more »

... or the development of alkylating chemotherapeutics. Used since the beginning of the 20th century, SM has been deployed in several conflicts around the world. It can lead to severe tissue damage - in particular dermal, mucosal, ocular and respiratory lesions - followed by impaired wound healing. While investigations of the acute toxicity have been the main focus up to now, explanations of long-term effects remain widely obscure. Increased understanding of the molecular mechanisms involved might help to identify new potential targets that could improve the general therapy of victims and the development of specific therapeutics. The ability of SM to cause lasting harm (e.g. cancer) and degenerative tissue damage after even a single exposure might - among other pathological processes - be explained by the involvement of underlying epigenetic modulations. The scientific field of epigenetics comprises alterations and modifications in gene expression that are not structurally changing the DNA sequence itself, but affecting chromatin organization as well as maintenance by e.g. DNA methylation and modifying histone patterns. SM is mainly used as a liquid or aerosolic chemical weapon agent (CWA) when dispersed, and directly interacts with tissues it comes into contact with first. As well as the aforementioned tissues, this interaction also involves corresponding small blood vessels. Blood vessel malformation (e.g. cherry hemangioma) is a frequent observation after SM exposure. Blood vessel formation depends on regeneration and immig [...]