Skin sensitization is a term used to refer to the regulatory hazard known as allergic contact dermatitis (ACD) in humans or contact hypersensitivity in rodents, an important health endpoint considered in chemical hazard and risk assessments. Information on skin sensitization potential is required in various regulatory frameworks, such as the Directive of the European Parliament and the Council on Registration, Evaluation and Authorization of Chemicals (REACH). The identification of skin-sensitizing chemicals previously required the use of animal testing, which is now being replaced by alternative methods. Alternative methods in the field of skin sensitization are based on the measurement or prediction of key events (KE), i.e., (i) the molecular triggering event, i.e., the covalent binding of electrophilic substances to nucleophilic centers in skin proteins; (ii) the activation of keratinocytes; (iii) the activation of dendritic cells; (iv) the proliferation of T cells. This review article focuses on the current state of knowledge regarding the methods corresponding to each of the key events in skin sensitization and considers the latest trends in the development and modification of these methods.
Abstract. Connexins and gap junctions play a crucial role during carcinogenesis. While diverse regulatory systems have been shown to modulate their function, the influence of cell motility on the intensity of gap junctional intercellular coupling has yet to be systematically addressed. Since cancer cell motility and intercellular coupling determine cancer development, we aimed at elucidating how mutual cell translocation modulates the intensity of gap junctional coupling in cell populations. Time-lapse analyses of the motility of connexin43 (Cx43)-coupled rat prostate carcinoma (MAT-LyLu) and mouse melanoma (B16) cells cultured on hyper-adhesive substrata revealed a reduced intensity of intercellular translocations in the two cell populations compared to the control conditions. While no detectable effects on the architecture of the actin cytoskeleton and Cx43 expression and phosphorylation were observed, the inhibition of cell motility was paralleled by an increase in the abundance of Cx43-positive plaques in cell-to-cell contacts and an enhancement of gap junctional coupling in cell populations cultured on hyper-adhesive substrata. Thus, a direct correlation between two cellular parameters crucial for carcinogenesis, i.e. cell motility and gap junctional coupling intensity exists in cancer cell populations.
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