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Effect of sulphur mustard on human skin cell lines with differential agent sensitivity
Author(s) -
Simpson Rachel,
Lindsay Christopher D.
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1044
Subject(s) - hacat , cell culture , sulfur mustard , viability assay , microbiology and biotechnology , cytotoxicity , cytotoxic t cell , dna damage , buthionine sulfoximine , mtt assay , cell , glutathione , chemistry , biology , biochemistry , toxicity , in vitro , dna , enzyme , genetics , organic chemistry
The ability of sulphur mustard (HD) to induce DNA damage places limits on the efficacy of approaches aimed at protecting human cells from the cytotoxic effects of HD using a variety of protective agents such as thiolcontaining esters and protease inhibitors. In the present study, potential alternative strategies were investigated by examining the differential effects of HD on G361, SVK14, HaCaT and NCTC 2544 human skin cells. The G361 cell line was more resistant to the cytotoxic effects of HD than the NCTC, HaCaT and SVK14 cell lines at HD doses of >3 and <100 µM HD as determined by the MTT assay. At 72 h after exposure to 60 µM HD there was up to an 8.8‐fold difference ( P < 0.0001) between G361 and SVK14 cell culture viability. Buthionine sulphoximine (BSO) pretreatment increased the sensitivity of all four cell lines to HD. A substantial proportion of the resistance of G361 cells to HD was attributable to BSO‐mediated effects on antioxidant‐mediated metabolism, although G361 cultures still retained a high degree of viability at 30 µM HD following BSO pretreatment. Cell cycle analysis confirmed that SVK14 cells were relatively more sensitive to HD, as shown by the 2.1‐fold reduction ( P < 0.0001) in the percentage of cells in G 0 [sol ]G 1 phase 24 h after HD exposure compared with control cultures. This compared well with a 1.2‐fold increase ( P < 0.05) in the percentage of G361 cells in G 0 [sol ]G 1 phase following HD exposure, suggesting the existence of a more efficient G 0 [sol ]G 1 checkpoint control mechanism in this cell line. Manipulation of the cell cycle using various modulating agents did not increase the resistance of cell lines to the cytotoxic effects of HD. © Crown copyright 2005. Published by John Wiley & Sons, Ltd.