The development of the Bhas42 cell transformation assay incorporating the human hepatic metabolic system for predicting a carcinogenicity of chemicals via hepatic metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08063
• 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: Kanagawa Institute of Industrial Sclence and Technology (2017); Kanagawa Academy of Science and Technology (2015-2016)
• Principal Investigator: Hirooka Takashi 地方独立行政法人神奈川県立産業技術総合研究所, 食品機能性評価グループ, 研究員(任期有) (50397519)
• Co-Investigator(Kenkyū-buntansha): 大森 清美 神奈川県衛生研究所, 理化学部, 主任研究員 (20416069)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 発がん性予測試験 / 細胞形質転換試験 / Bhas42 細胞 / 肝代謝 / ヒト肝細胞株 / 発がんプロモーター / 代謝活性化 / CYP酵素

Outline of Final Research Achievements

The Bhas42 cell transformation assay (Bhas42 CTA) has been internationally certified as an in vitro test method for predicting of chemical carcinogenicity. The purpose of this study is the development of the cell transformation assay using Bhas42 cells co-cultured with human hepatocytes for predicting the carcinogenicity of chemicals metabolized by hepatic metabolism system. We made the modified Bhas42 CTA medium, in which the CYP 3A4 activity of the human hepatocyte could be maintained at a detectable level for 10 days. Moreover, significantly increase in the formation of focus wasn’t observed in Bhas42 cells cultured with the modified CTA medium in the absence of test chemicals. On the other hand, we showed the expression of CYP1A1, 1A2 and 2B6 in Bhas42 cells by western blot analysis and CYP activity assay, and further demonstrated the contribution of CYP activities to focus formation of Bhas42 cells in initiation assay of 3-methylcholanthrene.

Free Research Field

環境毒性学