Metabolic transformation of indeno[1,2,3-cd]pyrene and toxicities of its metabolites.
A porphyrin/peroxynitrite biomimetic system was used to study the metabolism of indeno[1,2,3-cd]pyrene (IND) induced by peroxynitrite. The metabolites were identified using high-performance liquid chromatography coupled with electro-spray ionization tandem mass spectrometry as OH-IND, IND-quinone and 2NO2-IND. By stopping the reaction at different stages, we discovered that IND was first transformed to IND-quinone and 2NO2-IND, which were then transformed to OH-IND. Mutation assays including Ames tests and cell transformation experiments showed enhancement of the mutagenicity after the activation by the peroxynitrite/Fe(III)porphyrin system. The results also showed that 2NO2-IND and IND-quinone played key roles in the mutagenicity of PAHs after metabolic activation.
College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China, luoyj@bjut.edu.cn.
Yunjing
Y
Luo
Shaohui
S
Li
Yuanbin
Y
She
Rugang
R
Zhong
Shufen
S
Zhang
Xuejing
X
An
D002273:Carcinogens / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004784:Environmental Monitoring / Q000379:methods; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry*; D030421:Peroxynitrous Acid; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D013234:Stem Cells; D053719:Tandem Mass Spectrometry
D002273:Carcinogens; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D011166:Porphyrins; D011721:Pyrenes; D030421:Peroxynitrous Acid; C030984:pyrene; C041508:indeno(1,2,3-cd)pyrene