This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Smith, C N Articles by Lindsay, C D Search for Related Content PubMed PubMed Citation Articles by Smith, C N Articles by Lindsay, C D Social Bookmarking                         What's this?

Stimulation of C32 and G361 melanoma cells using oleoyl acetyl glycerol and its effect on sulphur mustard cytotoxicity

C D Lindsay

Biomedical Sciences Department, Dstl Chemical and Biological Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK

Epidermal melanocytes have a higher sensitivity to sulphur mustard (HD) compared with other skin cell types.¹ This may be due to the enzymatic production of melanin precursors exerting an additional cytotoxic effect following HD depletion of the cellular protectant, GSH.^2,3 Stimulation of the protein kinase C pathway in melanocytes is known to increase melanin production in melanocytes and melanoma cell lines.^4,5 In order to investigate the role of pigment synthesis in HD toxicology, cultures of an unpigmented melanoma cell line (C32) and of a pigmented melanoma line (G361) were treated with the potent diacyl glycerol analogue, oleoyl acetyl glycerol (OAG), in order to determine if protein kinase C-mediated increases in pigment production could increase sensitivity to subsequent HD exposure. Stimulation of C32 cells with OAG exerted a significant protective effect against the cytotoxic effects of HD. However, this was not due to increased melanin synthesis because this cell line cannot synthesize melanin pigments. The protective action observed is postulated to be due to modulation of protein kinase C activity. In contrast, stimulation of G361 melanoma cells with OAG resulted in an increased level of cytotoxicity upon subsequent exposure to HD. Protein kinase C controls several cellular pathways including checkpoints in the cell cycle, stalling the cell in G₁ and promoting transition through the G₂ /M boundary. Given the genotoxic properties of HD, these two points in the cell cycle are important in determining the overall cytotoxic effect of HD. Control of the cell cycle by protein kinase C modulation and manipulation of melanin synthetic pathways may have therapeutic benefits.

Key Words: sulphur mustard • melanoma • cell cycle • protein kinase C • diacyl glycerol

Human & Experimental Toxicology, Vol. 20, No. 8, 418-425 (2001)
DOI: 10.1191/096032701682692991


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?