Bhat, K., B. Benton, and R. Ray. DNA Ligase Activation Following Sulfur Mustard Exposure in Cultured Human Epidermal Keratinocytes. In Vitro Molec. Toxicol. 1998. 11(1): 45-53.

sulfur mustard - 00505-60-2

DNA ligase is a key enzyme involved in DNA repair. In cultured normal human epidermal keratinocytes (NHEK), the alkylating agent sulfur mustard (bis-(2-chloroethyl)sulfide, HD) caused a rapid (within 30 min) and dose-dependent DNA ligase activation followed by an exponential decay. The decay rate decreased by 60% in the presence of 3-aminobenzamide (3-AB), an inhibitor of poly (ADP-ribose) polymerase (PARP), or in that of the Ca²⁺ chelators EGTA (ethylene glycol-bis (amino ethyl ether) N,N,N',N'-tetraacetic acid) and BAPTA AM (1,2 Bis(2-amino-phenoxy)(methane N,N,N',N'-tetraacetic acid), tetraacetoxy methyl ester). The activated enzyme was found to be a protein of approximately 130 kD. A qualitative agarose gel analysis of DNA extracted from HD-exposed NHEK showed a progressive increase in high molecular weight DNA, suggesting DNA repair. This knowledge of the DNA repair in the HD-exposed NHEK model may be useful in developing protective measures against skin damage by HD.