Development of a screening system for immunotoxic chemicals considering metabolic activation in skin

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Azabu University
• Principal Investigator: SEKIMOTO Masashi 麻布大学, 生命・環境科学部, 准教授 (10381732)
• Research Collaborator: MATSUSHITA Marimo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫毒性 / 皮膚感作性 / レポーターアッセイ / 異物代謝酵素

Outline of Final Research Achievements

In this study, we aimed to analyze the role of xenobiotic metabolizing enzymes in immunotoxic response in skin by skin-sensitizers. As a result of transfecting various reporter genes into human skin keratinocyte HaCaT cells and evaluating its usefulness, it was shown that HaCaT-Nrf2-Luc cells as a useful cell line for analysis of skin immunotoxicity. The role of xenobiotic metabolizing enzymes in immunotoxicity by skin-sensitizers using this cell line were examined. As a result, it was suggested that the immunotoxicity of some skin-sensitizers are changed by activation/detoxification of chemicals by P450 enzymes expressed in HaCaT cells.

Free Research Field

分子毒性学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、皮膚細胞内に発現している異物代謝酵素が化学物質の免疫毒性発現に重要な役割を果たしていることが示された。本研究結果は、より高精度な iv vitro 免疫毒性試験（動物を使用しない試験）の確立に繋がる。また、本研究をさらに発展させることにより、異物代謝酵素の遺伝子多型によって起こるであろう免疫毒性反応（≒アレルギー反応）の個人差を予測・解析する上で新たな知見をもたらすことが期待される。