This controlled, blinded study did not replicate the results of previous reports of microdysgenesis in IGE. Although factors such as syndrome heterogeneity and sample size may explain the discrepancy, technical factors could also play a role. The current ion channel hypothesis for the pathogenesis of IGE does not preclude microscopic or ultramicroscopic abnormalities and the search for these should continue.

Summary The chemical carcinogen 7,12-dimethylbenz (a) anthracene (DMBA) is a potent carcinogen which, when applied to the skin of BALB/c mice weekly for 7-8 weeks, causes the induction of macroscopically visible skin tumours. We report that DMBA also depletes Langerhans cells (LC) the chemical carcinogen 7,12-dimethylbenz (a) anthracene (DMBA) on LC numbers and morphology as assessed by adenosine triphosphatase (ATPase) staining during the induction and growth of DMBA-induced skin tumours. DMBA caused depletion of LC from skin surrounding the tumours, and the LC reappeared as the tumours ceased growing. The time scale of reappearance of LC suggests they were being repopulated from bone-marrow derived precursors. Materials and methodsCarcinogen treatment of mice Male BALB/c mice were obtained from Walter and Eliza Hall Institute, Melbourne; from 8-9 weeks of age they were treated with 7,12-dimethylbenz (a) anthracene (DMBA, Sigma, USA, Lot 24F-0052) as described by Muller & Flannery (1973). The dorsal trunk skin of the mice was shaved with electric clippers and painted with 1% DMBA dissolved in equal volumes of lanoline (Sigma, USA) and liquid paraffin (Supply and Tender, Hobart); control mice received solvent alone.To determine the early effects of DMBA on LC before tumours became apparent, groups of 4 mice were treated with DMBA. The first application of DMBA was designated as being on day 0, with weekly applications for up to 4 weeks; mice being killed 3 or 7 days following the last treatment. To determine the LC density in DMBA-treated skin during growth of DMBA-induced tumours, the DMBA was applied weekly for 7-8 weeks, the final application of DMBA was designated as being on day 0.(J The

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