Elucidation of novel benzo (a) pyrene DNA adduct formation mechanism and search for genotoxicity preventive foods.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06736
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Nihon University
• Principal Investigator: UNO Shigeyuki 日本大学, 医学部, 講師 (90307851)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ベンゾ(a)ピレン / DNA付加体

Outline of Final Research Achievements

Since the involvement of molecules other than CYP1A1 in the genotoxicity (DNA adduct formation) of the carcinogen benzo (a) pyrene (BaP) was clarified, we attempted to elucidate the detailed mechanism. We also established a simple DNA adduct detection method. By using the waveguide mode sensor of the optical sensing system, it became possible to quickly detect BPDE DNA adducts in BaP-treated mouse liver and cultured cells. It was also shown that molecules other than CYP1A1 are involved in the 9,10-epoxy reaction of BaP DNA adduct formation. Furthermore, DATS, a garlic component with anticancer activity, increased BaP DNA adducts. It was suggested that DATS acts on a mechanism other than DNA adduct formation.

Free Research Field

毒性学

Academic Significance and Societal Importance of the Research Achievements

BaPの遺伝毒性の主要因であるBPDEのDNA付加体形成の検出法は32Pポストラベル法が主流であるが、時間とコストがかかり、多量サンプルの解析に向いていない。本研究で確立した光センシングシステムの導波モードセンサーを利用した新たな簡便かつ迅速なBPDEのDNA付加体検出法は、マルチチャンネル型の導波モードセンサーの開発も可能であり1次スクリーニング法としては有用な検出法になると考える。また、がんに対する治療は、抗がん剤に対する抵抗性、再発など問題点が多く、がん予防の重要性が指摘されている。そこでDNA付加体形成の詳細な検討は予防法の確立を考える上で重要な知見になると考える。