University of Tasmania

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Immunomodulation of Langerhans cells by chemical carcinogens : implications for tumour development

posted on 2023-05-27, 18:02 authored by Qu, Miaomiao
Application of the chemical carcinogen 7 ,12-dimethylbenz(a)anthracene (DMBA) to murine skin causes tumour development as well as damaging the skin immune system (SIS). Langerhans cells (LC), the major component of the SIS are depleted from DMBA treated skin. The overall aim of this thesis was to analyse the interaction of chemical carcinogens with the LC and to determine the significance of this carcinogen-caused LC depletion in tumour development. Analysis of the immune response to DMBA revealed similarities to a normal antigen. Although BALB/c (H-2d) mice responded poorly to DMBA, this carcinogen induced a contact hypersensitivity response (CHS) in C3H/HeN(H-2k) mice, was trapped by the LC in the skin and cells bearing DMBA were detected in the draining lymph nodes. The tumour promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) was also found to be antigenic as it induced a strong CHS response in BALB/c mice as did the contact sensitisers (antigens). A significant decrease in LC number was caused by the chemical carcinogens DMBA and TPA as well as by the antigens. This LC depletion was found to be dose dependent and immune tolerance was induced following application of a second antigen through skin depleted of LC. Consequently carcinogen and antigen induced depletion both lead to tolerance. This suppression was cell mediated, because it was adoptively transferred by spleen cells to naive syngeneic mice. The effect of LC depletion on the pathogenesis of skin cancer was evaluated. A low dose (initiating dose) of DMBA that did not cause LC depletion also failed to cause tumour development. This initiating dose of DMBA followed by multiple applications of LC depleting doses of the antigen TNCB or the promoter TP A induced tumour growth. Consequently the LC depleting dose of antigen functioned as a tumour promoter. An application of the depleting dose of TNCB, when followed by a large dose of DMBA (a complete carcinogen) accelerated tumour development. Thus LC depletion, irrelevant to the causes, may impair immunosurveillance.


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Copyright 1995 the author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s). Includes bibliographical references. Thesis (M.Med.Sc.)--University of Tasmania, 1995

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