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Induction chimique de tumeurs cutanées chez la souris Hairless SKH-1 en vue de photochimiothérapie

Abstract : The number of skin cancers being in constant progression during the last few years, it is necessary to develop some representative skin tumor models of human pathology in order to test the validity of new therapeutic methods as photochemotherapy. Skin tumor models such as papillomas or carcinomas in Hairless mice have been obtained by a two- or a three-step carcinogenesis process using an initiator (DMBA), a promoter (TPA) and a conversion agent (4-NQO) for the second protocol. Moreover, the skin carcinoma model has allowed to develop an original syngenic model of subcutaneous epithelial carcinomas. The benign or ma lignant nature of the skin tumors produced with a chemical carcinogenesis process has been determined by a phatological study. Otherwise, the epithelial nature of carcinomatous cells isolated from squamous-cell carcinomas chemically induced, has been confirmed by microscopical observations and immunohistochemical studies using anti-keratin rabbit antibodies. Fluorescence spectroscopy has allowed to establish autofluorescence spectra of the normal skin and the different type of tumors, and also to follow the skin modifications occuring during the chemical skin carcinogenesis process in a diagnostic purpose. Thus, it has been possible to predict in 78% of the cases the tumor apparition. This non-invasive method has been used to follow the biodistribution of two photosensitizers (mTHPC and HpD injected by i.p. in Hairless mice) for papillomas and carcinomas. These kinetics seem to be charaterized by two maxima: a first pick occuring rapidly and an other more late, but more high. These maximal ratios have been estimated: the papilloma/normal skin ratio = 6,2 ± 2,7 for HpD and 5,1 ± 1,6 for m-THPC and the carcinoma/normal skin ratio = 3,2 ± 1,4 for HpD and 2,7 ± 2,1 for m-THPC. This kinetic in two maxima seem to be confirmed by fluorescence microscopy with image analysis. The results of the se biodistribution studies will be used to carry out photodynamic therapy in Hairless mice bearing skin tumors in order to estimate the efficiency of the two photosensitizers.
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Submitted on : Thursday, March 29, 2018 - 10:56:50 AM
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Edwige Bossu. Induction chimique de tumeurs cutanées chez la souris Hairless SKH-1 en vue de photochimiothérapie. Biologie animale. Université Henri Poincaré - Nancy 1, 1999. Français. ⟨NNT : 1999NAN19904⟩. ⟨tel-01747298⟩



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