Quantification of the co-mutagenic β-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods

Totsuka, Yukari; Ushiyama, Hirofumi; Ishihara, Junko; Sinha, Rashmi; Goto, Sumio; Sügimura, Takashi; Wakabayashi, Keiji

doi:10.1016/s0304-3835(99)00143-3

Cited by 134 publications

(88 citation statements)

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“…While we expected levels of APNH in urine from smokers to be much higher than those of nonsmokers, given the presence of norharman and aniline in tobacco smoke (1,17), no significant difference was in fact observed (195 F 154 pg versus 161 F 181 pg, respectively). Comparison of norharman and aniline levels in human urine samples between smokers and nonsmokers also showed no significant differences.…”

Section: Discussionmentioning

confidence: 97%

“…It has been reported that norharman is produced by pyrolysis of tryptophan (18) and is present at high levels in cigarette smoke condensate and various kinds of cooked foods (1). Moreover, norharman is known to be formed endogenously and be detectable in human urine samples from both healthy volunteers eating an ordinary diet and patients receiving parenteral alimentation (12,19).…”

Section: Discussionmentioning

confidence: 99%

“…The appearance of mutagenicity was caused by the formation of various mutagenic compounds [i.e., aminophenyl-h-carbolines, such as 9-(4 ¶-amino-3 ¶-methylphenyl)-9H-pyrido[3,4-b]indole, 9-(4 ¶-amino-3 ¶-methylphenyl)-1-methyl-9H-pyrido[3,4-b]indole, and 9-(4 ¶-aminophenyl)-1-methyl-9H-pyrido [3,4-b]indole (25,26)]. Because harman and o-toluidine are also widely distributed in the environment (1,17,27), humans could be continuously exposed, and aminophenyl-h-carbolines are also probably formed in the human body.…”

Section: Discussionmentioning

confidence: 99%

“…9H-pyrido [3,4-b]indole (norharman), widely distributed in our environment, such as in cigarette smoke and cooked foods (1), is not mutagenic to Salmonella typhimurium strains, either with or without S9 mix. However, it becomes mutagenic to S. typhimurium TA98 and YG1024 with S9 mix in the copresence of nonmutagenic aromatic amines, such as aniline and o-toluidine (2-4).…”

Section: Introductionmentioning

confidence: 99%

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Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples

Nishigaki

Totsuka

Kataoka

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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 Mg for smokers and 52 to 447 ng and 0.49 to 5.72 Mg 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 Mg 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. (Cancer Epidemiol Biomarkers Prev 2007; 16(1):151 -6)

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples

Nishigaki

Totsuka

Kataoka

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Using this experimental model, both initiation and promotion activity of pancreatic duct can be examined 10,11 . Norharman (9H-pyrido [3,4-b]indole) is produced in the pyrolysis of tryptophan and reported to be present in alcoholic beverages like beer, wine, sake or whisky, as well as in cigarette smoke condensate, cooked meat and fish [12][13][14][15] . Previously, it has been reported that, norharman itself is not a mutagen in Salmonella typhimurium TA98 and TA100, either with or without a metabolic activation system (S9 mix) 16 , but becomes mutagenic to S. typhimurium TA98 with S9 mix when incubated with non-mutagenic aromatic amines, such as aniline or o-toluidine 17 .…”

Section: Introductionmentioning

confidence: 99%

Possible Lack of Carcinogenic Potential of 9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorbarman) for the Pancreatic Duct Epithelium in Hamsters.

et al. 2002

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Abstract:The carcinogenic potential of 9-(4'-aminophenyl)-9H-pyrido [3,4-b]indole (aminophenylnorharman: APNH), a newly identified heterocyclic amine, was evaluated in a rapid production model for pancreatic duct adenocarcinoma in hamsters. In experiment 1, the initiation potential of APNH was examined. Hamsters received corn oil, 30 mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) or APNH (totally 50 and 100 mg/kg) as initiators followed by two cycles of augmentation pressure for pancreatic duct carcinogenesis and were sacrificed 75 to 78 days after the beginning of the experiment. Ductal hyperplasia and atypical hyperplasias developed in hamsters receiving APNH but their numbers and incidences did not differ from the corn oil case. In experiment 2, promoting potential of APNH for pancreatic duct carcinogenesis was examined. Hamsters received 30 mg/kg body weight BOP as an initiator followed by augmentation pressures and thereafter diet containing 0, 25 or 50 ppm APNH for 50 days. All hamsters were sacrificed 100 days after the beginning of the experiment. The numbers and incidences of ductal lesions, including adenocarcinomas, did not differ among the experimental groups. The results suggest, APNH may not have initiation or promotion potential for pancreatic duct carcinogenesis in hamsters. (J Toxicol Pathol 2002; 15: 7-12)

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Monozyklische aromatische Amino‐ und Nitroverbindungen [MAK Value Documentation in German language, 2003]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 37. Lieferung, Ausgabe 2003 Der Artikel enthält folgende Kapitel: Einleitung Einstufung Toxizität Hinweise auf nicht‐genotoxische Effekte Genotoxizität In vitro In vivo Tumorentstehung Wirksamkeit Diskussion Wirkungsmechanismus Struktur‐Wirkungs‐Beziehungen Der Einfluss der Stellungsisomerie Analogien zwischen Arylaminen und Nitroverbindungen Die Gemeinsamkeiten Die Unterschiede Folgerungen für die Einstufung Schlussfolgerungen Ausblick

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Quantification of the co-mutagenic β-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods

Cited by 134 publications

References 13 publications

Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples

Detection of Aminophenylnorharman, a Possible Endogenous Mutagenic and Carcinogenic Compound, in Human Urine Samples

Possible Lack of Carcinogenic Potential of 9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorbarman) for the Pancreatic Duct Epithelium in Hamsters.

Monozyklische aromatische Amino‐ und Nitroverbindungen [MAK Value Documentation in German language, 2003]

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