Fletchera, S.T., Bakera, V.A., Fentema, J.H., Baskettera, D.A., Kelsellb, D.P. aSEAC Toxicology Unit, Unilever Research, Sharnbrook, Bedfordshire MK44 1LQ, UK. bCentre for Cutaneous Research, St Bartholomews and The Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK.

There is a need to investigate the mechanistic basis of the human skin irritation response if relevant in vitro test systems for the predictive identification of skin irritation hazards are to be developed. Recent progress in genomics technologies mean that tools for the identification and investigation of important biochemical events in the processes of skin irritation are now available. The aim of this work was to identify genes (for further mechanistic investigation) which may be regulated in response to skin irritation, following exposure of the EpiDerm skin model to the known skin irritant sodium lauryl sulphate (SLS). EpiDerm cultures were treated in triplicate with a non-cytotoxic dose of SLS (0.1 mg/ml, as determined by the MTT assay and histological examination) for 15 min, 30 min, 1 h, 2 h, 3 h, 4 h and 24 h. Total RNA was extracted from the pooled EpiDerm cultures and used to probe Atlas™ human arrays (Clontech) covering approximately 3600 genes. Preliminary data indicated an up-regulation at early time points (15–30 min) of a number of genes involved in transportation (e.g. the sodium and chloride dependent taurine transporter) and receptors (e.g. ZAP70 and protocadherin 42 precursor). The gene encoding the UV excision repair protein and other DNA repair genes (e.g. DNA-directed RNA polymerase II) were up-regulated after 1–3 h, along with TGFb3 and other tumour suppressors, which play a role in cellular development and wound healing. At the later time points of 4–24 h, genes involved in protein translation (e.g. Cathepsin D receptor) and metabolism (e.g. CYP27A) were up-regulated. In addition, a number of genes were down-regulated in response to treatment with SLS, although these followed less of a time dependent pattern. These results indicate the differential regulation of a number of genes in response to treatment with SLS, some of which may provide additional clues to the molecular events underpinning the irritation response to this particular surfactant and possibly to other chemical irritants.


2AP70, CDNA, CDNA microarrays, CYP27A, Cathepsin D, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Cytotoxicity, Dermal irritancy, Dermal irritancy testing, Dermal irritation, EpiDerm, Gene expression, Genomic technologies, Genomics, Metabolism, Microarray, Photocacherin 42 precursor, RNA, RNA, Isolation of, Skin irritancy, Skin irritation, TGF-beta-3, TH2 cytokines, UV light, cDNA, cDNA microarrays

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