Cellular macromolecules in exposed tissue

Cellular macromolecules in exposed tissue refers to the collective group of essential biological polymers—including DNA, RNA, proteins, and lipids—that serve as the primary targets for reactive chemical agents and ionizing radiation in tissues directly contacted by these stressors. This concept is central to the toxicology of vesicants like sulfur mustard and nitrogen mustard, which act as potent bifunctional alkylating agents. These agents form highly reactive electrophilic intermediates that covalently bind to nucleophilic sites on cellular macromolecules, most notably the N7 position of guanine in DNA, leading to the formation of adducts and interstrand cross-links. Such modifications disrupt critical cellular processes, including DNA replication and protein synthesis, triggering signaling cascades that lead to cell cycle arrest, apoptosis, and the characteristic inflammatory blistering (vesication) of the skin, eyes, and respiratory tract. In addition to their role in toxicity, these macromolecules are the therapeutic targets for nitrogen mustard-derived chemotherapeutic drugs, such as mechlorethamine, which exploit the same alkylating mechanism to induce lethal DNA damage in cancer cells. Protective and therapeutic strategies against macromolecular damage include the use of nucleophilic scavengers like sodium thiosulfate to neutralize agents before they react, as well as antioxidants like N-acetylcysteine to mitigate secondary oxidative damage.

Other names

Cellular macromoleculesBiological macromoleculesTarget macromoleculesDNA, proteins, and lipids in exposed tissuesSubcellular components

Alkylation of nucleophilic sites in DNA, proteins, and lipids; formation of DNA interstrand cross-links; induction of oxidative stress and lipid peroxidation; depletion of cellular glutathione.