title: Investigation of the genotoxic effects of 2-amino-9H-pyrido[2,3-b]indole in different organs of rodents and in human derived cells.
abstract: Aim of the present study was the investigation of the genotoxicity of amino-alpha-carboline (AalphaC) in human derived cells and of its organ-specific effects in laboratory rodents. This heterocyclic amine (HA) is contained in fried meat and fish in higher concentrations than most other cooked food mutagens. In the present experiments, AalphaC caused dose-dependent induction of micronuclei in the human derived hepatoma cell line HepG2 at concentrations > or =50 microM. In contrast, no significant effects were seen in Hep3B, another human hepatoma cell line, which may be explained by the concurrent lower activity of sulfotransferase (SULT), an enzyme playing a key role in the activation of AalphaC. A positive result was also obtained in the single cell gel electrophoresis (SCGE) assay in peripheral human lymphocytes, but the effect was only significant at the highest concentration (1000 microM). In Fischer F344 rats and ICR mice, the liver was the main target organ for the formation of DNA adducts (at > or =50 mg/kg bw), and in lungs and colon substantially lower levels were detected. Identical organ specificity as in the DNA adduct measurements was seen in SCGE assays with rats, whereas in mice the most pronounced induction of DNA migration was observed in the colon. Comparison of our results with data from earlier experiments indicate that the genotoxic potency of AalphaC is equal to that of other HAs, which are contained in human foods in much smaller amounts. Therefore, our findings can be taken as an indication that the human health risk caused by exposure to AalphaC is higher than that of other HAs that are formed during the cooking of meat and fish.
authors.affiliation: Institute of Cancer Research, University of Vienna, Borschkegasse 8A, A-1090 Vienna, Austria.
authors.forename: B J
authors.initials: BJ
authors.lastname: Majer
authors.forename: F
authors.initials: F
authors.lastname: Kassie
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: W
authors.initials: W
authors.lastname: Pfau
authors.forename: H
authors.initials: H
authors.lastname: Glatt
authors.forename: W
authors.initials: W
authors.lastname: Meinl
authors.forename: F
authors.initials: F
authors.lastname: Darroudi
authors.forename: S
authors.initials: S
authors.lastname: Knasmüller
mesh_terms: D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000737:chemistry; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002243:Carbolines; D018736:DNA Adducts; D009153:Mutagens; D004247:DNA; C017822:2-amino-9H-pyrido(2,3-b)indole