title: Detection of aminophenylnorharman, a possible endogenous mutagenic and carcinogenic compound, in human urine samples.
abstract: Mutagenic/carcinogenic 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman (APNH)] is formed from norharman and aniline in the presence of cytochrome P450 3A4/1A2. Because both precursors are widely distributed in the environment, human exposure is unavoidable. To clarify APNH formation in the human body, amounts of the compound in 24-h human urine collected from smokers and nonsmokers, eating a normal diet, were analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry. In addition, norharman and aniline were also analyzed by high-performance liquid chromatography and gas chromatography, respectively. APNH could be detected in all urine samples at levels 49 to 449 pg for smokers and 21 to 594 pg for nonsmokers per 24-h urine, respectively. The amounts of norharman and aniline were 46 to 185 ng and 0.70 to 8.10 microg for smokers and 52 to 447 ng and 0.49 to 5.72 microg for nonsmokers, respectively, per 24-h urine (none of the levels differing significantly between smokers and nonsmokers). To exclude exogenous exposure to norharman and aniline, we analyzed the levels of APNH, norharman, and aniline in urine samples collected from inpatients receiving parenteral alimentation. Similar to the healthy volunteers, all urine samples contained 12 to 338 pg of APNH, 6 to 75 ng of norharman, and 0.33 to 1.86 microg of aniline per 24-h urine. These results suggest that APNH should be considered as a novel endogenous mutagen/carcinogen; thus, it is very important to determine the biological significance of this carcinogen for human cancer development.
authors.affiliation: Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Rena
authors.initials: R
authors.lastname: Nishigaki
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Ushiyama
authors.forename: Sumio
authors.initials: S
authors.lastname: Goto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akasu
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000328:Adult; D000814:Aniline Compounds / Q000652:urine*; D002243:Carbolines; D002273:Carcinogens / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000652:urine; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D007211:Indoles / Q000652:urine*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D011725:Pyridines / Q000652:urine*; D012907:Smoking / Q000652:urine
chemical_list: D000814:Aniline Compounds; D002243:Carbolines; D002273:Carcinogens; D007211:Indoles; D009153:Mutagens; D011725:Pyridines; D006247:Harmine; D003577:Cytochrome P-450 Enzyme System; C010262:norharman; C421010:9-(4'-aminophenyl)-9H-pyrido(3,4-b)indole; C023650:aniline