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首页> 外文期刊>Archives of Toxicology >Biotransformation of 2,4-toluenediamine in human skin and reconstructed tissues
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Biotransformation of 2,4-toluenediamine in human skin and reconstructed tissues

机译：人体皮肤和重建组织中2,4-甲苯胺的生物转化

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Reconstructed human epidermis (RHE) is used for risk assessment of chemicals and cosmetics and RHE as well as reconstructed human full-thickness skin (RHS) become important for e.g., the pre-clinical development of drugs. Yet, the knowledge regarding their biotransformation capacity is still limited, although the metabolic activity is highly relevant for skin sensitization, genotoxicity, and the efficacy of topical dermatics. The biotransformation of the aromatic amine 2,4-toluenediamine (2,4-TDA) has been compared in two commercially available RHS to normal human skin ex vivo, and in primary epidermal keratinocytes and dermal fibroblasts as well as in vitro generated epidermal Langerhans cells and dermal dendritic cells. The mono N-acetylated derivative N-(3-amino-4-methylphenyl) acetamide (M1) was the only metabolite detectable in substantial amounts indicating the predominance of N-acetylation. RHS exceeded human skin ex vivo in N-acetyltransferase activity and in cell cultures metabolite formation ranked as follows: keratinocytes > fibroblasts similar to Langerhans cells similar to dendritic cells. In conclusion, our results underline the principal suitability of RHS as an adequate test matrix for the investigation of N-acetylation of xenobiotics which is most relevant for risk assessment associated with cutaneous exposure to aromatic amines.
机译：重建的人表皮（RHE）用于化学品和化妆品的风险评估，以及重建的人全厚皮（RHS）对例如，药物前期临床开发是重要的。然而，对于它们的生物转化能力的知识仍然有限，尽管代谢活性对皮肤致敏，遗传毒性和局部皮肤的功效非常相关。已经将芳族胺2,4-甲苯二胺（2,4-TDA）的生物转化在两种商业上可获得的RHS中与正常人体皮肤进行比较，以及在原发性表皮角质形成细胞和皮肤成纤维细胞以及体外产生的表皮朗格汉斯细胞中和皮肤的树突细胞。单乙酰化衍生物N-（3-氨基-4-甲基苯基）乙酰胺（M1）是唯一可检测的代谢物，其大量可检测，表明正乙酰化的优势。 RHS超过了N-乙酰转移酶活性的人体皮肤，在N-乙酰转移酶活性和细胞培养物中，代谢物形成排名如下：角质形成细胞>类似于类似树突细胞的朗格汉斯细胞的成纤维细胞。总之，我们的结果强调RHS作为足够试验基质的rHS的主要适用性，用于研究异丙苯的N-乙酰化，其对与芳香胺的皮肤暴露有关的风险评估最相关。

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