Kojic acid reduces the cytotoxic effects of sulfur mustard on cultures containing human melanoma cells in vitro

In vivo experiments have shown that melanocytes are more sensitive than ker atinocytes to the cytotoxic effects of sulfur mustard when it is applied to pically to pig skin.(1) It has been hypothesized that this is caused by the uncoupling of the melanogenic pathway by depletion of cellular glutathione , resulting in the uncontrolled production of cytotoxic quinone free-radica l species by tyrosinase.(2) In the present study, the feasibility of blocki ng the melanogenic pathway as a means of reducing the cytotoxicity of sulfu r mustard was evaluated using kojic acid. Kojic acid is a topically applied depigmenting agent that exerts its effect by acting as a slow-binding, com petitive inhibitor of tyrosinase.(3) Preincubation of G361 pigmented melano ma cells and mixed cultures of G361 cells and SVK keratinocytes with 2.5 mM kojic acid resulted in significant increases in the viability of these cul tures as determined by neutral red (NR) and gentian violet (GV) dye binding assays for up to 48 h following exposure to 50 muM sulfur mustard. The hig hest levels of protection were seen in the G361 cultures, with a 26.8% incr ease in culture viability (NR assay) compared with the sulfur-mustard-only controls at 24 h. Preincubation of SVK cells alone with kojic acid resulted in lower increases in viability (2.5% at 24 h by the NR assay). Inhibition of the melanogenic pathway reduces the sensitivity of cultures containing pigment cells to sulfur mustard. (C) Crown copyright 2001. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.