変異・癌原性物質の産生・代謝とその活性抑制に関する研究
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概要
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Dr Bruce Ames developed a simple procedure for assaying bacterial mutation, i.e. the Ames test, using Salmonella Typhimurium his mutant strains. We have used this procedure to measure mutagenicity of complex mixtures such as those in airborne particulates, automobile exhaust, small engine exhaust, wastewater, kerosene-heater exhaust and yakitori as well as nitroarenes in the mixtures, especially 1-nitropyrene(1-NP) and dinitropyrenes(diNPs). We measured the amounts of 1-NP and diNPs by a new procedure in which specific nitroreductases are used to convert NP to aminopyrene(AP) and the fluorescent AP is assayed efficiently and sensitively by high-pressure liquid chromatography. Metabolism of 1-NP in germ-free and conventional rats was elucidated: it appears that the liver is primarily responsible for ring hydroxylation and N-acetylation of 1-NP and for O-glucuronide conjugation, while intestinal bacteria play a dominant role in nitroreduction of 1-NP and its metabolites and in glucuronide cleavage. In addition, we showed that glutathione conjugates of 1-NP oxides produced in the liver were excreted into the bile and those in the upper intestine were metabolized to the corresponding cysteinylglycine and cysteine conjugates by γ-glutamyl-transferase and aminopeptidase of pancreatic juice. The cysteine conjugates were then metabolized by β-lyase of the normal bacterial flora in the lower intestine to the reactivated metabolites and reabsorbed, partly producing DNA adducts in the intestinal mucosa. We observed in vivo formation of mutagens induced by intraperitoneal administration of pyrene in animals during exposure to nitrogen dioxide, and we concluded that 1-hydroxypyrene is nitrated in the body when the animal is exposed to NO_2 gas after hydroxylation of pyrene in the liver. We studied the carcinogenicity of 1,6-diNP, which is stronger than that of benzo [α] pyrene, the augmenting effect of a nonmutagenic fraction in soy sauce on mutagenicity of 3-diazotyramine produced in nitrite-treated soy sauce, the antimutagenicity and anticarcinogenicity of spices and medicinal plants, lemon grass(Cymbopogon citratus Stapf), roselle (Hibiscus sabdariffa Linn.), bitter melon(Momordica charantia Linn.) and Murdannia loriformis, and the interaction among drugs, antibiotics and intestinal bacteria. We developed new bacteria that produce lycopene or human lactoferrin, which are chemopreventive substances.
- 日本環境変異原学会の論文
- 2002-09-30
著者
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大西 克成
徳島大学大学院医学研究科
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大西 克成
徳島大学大学院ヘルスバイオサイエンス研究部生体制御医学講座分子細菌学分野
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大西 克成
徳島大学大学院医学研究科プロテオミクス医科学専攻生体制御医学講座分子細菌学分野
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- 変異・癌原性物質の産生・代謝とその活性抑制に関する研究