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Titolo:
Genotoxic effects of heterocyclic aromatic amines in human derived hepatoma (HepG2) cells
Autore:
Knasmuller, S; Schwab, CE; Land, SJ; Wang, CY; Sanyal, R; Kundi, M; Parzefall, W; Darroudi, F;
Indirizzi:
Univ Vienna, Inst Canc Res, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 Inst Canc Res, A-1090 Vienna, Austria Karmanos Canc Inst, Mol & Chem Carcinogenesis Program, Detroit, MI USA Karmanos Canc Inst Detroit MI USA arcinogenesis Program, Detroit, MI USA SUNY Hlth Sci Ctr, Dept Urol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr Syracuse NY USA 13210 Dept Urol, Syracuse, NY 13210 USA Univ Vienna, Inst Environm Hyg, Vienna, Austria Univ Vienna Vienna Austria v Vienna, Inst Environm Hyg, Vienna, Austria Leiden State Univ, Med Ctr, Dept Radiat Genet & Chem Mutagenesis, MGC, Leiden, Netherlands Leiden State Univ Leiden Netherlands agenesis, MGC, Leiden, Netherlands
Titolo Testata:
MUTAGENESIS
fascicolo: 6, volume: 14, anno: 1999,
pagine: 533 - 539
SICI:
0267-8357(199911)14:6<533:GEOHAA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
SALMONELLA-TYPHIMURIUM STRAINS; SISTER-CHROMATID EXCHANGES; CULTURED MAMMALIAN-CELLS; CHINESE-HAMSTER CELLS; COOKED-FOOD MUTAGENS; METABOLIC-ACTIVATION; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; BEEF EXTRACT; CHROMOSOME-ABERRATIONS; QUANTITATIVE STRUCTURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Knasmuller, S Univ Vienna, Inst Canc Res, Borschkegasse 8A, A-1090 Vienna,Austria Univ Vienna Borschkegasse 8A Vienna Austria A-1090 Austria
Citazione:
S. Knasmuller et al., "Genotoxic effects of heterocyclic aromatic amines in human derived hepatoma (HepG2) cells", MUTAGENESIS, 14(6), 1999, pp. 533-539

Abstract

In order to study the mutagenic effects of heterocyclic aromatic amines (HAAs) in cells of human origin, five compounds, namely 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), the pyridoimidazo derivative 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and 3-amino-1,4- dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were tested in micronucleus (MN) assays with a human derived hepatoma (HepG2) cell line. All HAAs caused significant, dose-dependent effects. The activities of IQ, MeIQ, MeIQx and PhIP were similar (lowest effective concentrations 25-50 mu M), whereas Trp-P-1 was effective at a dose of greater than or equal to 2.1 mu M. In addition, the HAAs were tested in MN assays with Chinese hamster ovary(CHO) cells and in Salmonella strain YG1024 using HepG2 cell homogenates as an activation mix. In the CHO experiments, positive results were obtainedwith Trp-P-1 and PhIP, whereas the other compounds were devoid of activityunder all experimental conditions. The discrepancy in the responsivity of the two cell lines is probably due to differences in their acetylation capacity: enzyme measurements with 2-aminofluorene as a substrate revealed thatthe cytosolic acetyltransferase activity in the HepG2 cells is similar to 40-fold higher than that of the CHO cells. In the bacterial assays all fiveHAAs gave positive results but the ranking order was completely different from that seen in the HepG2/MN experiments (IQ > MeIQ > Trp-P-1 greater than or equal to MeIQx >> PhIP) and the mutagenic potencies of the various compounds varied over several orders of magnitude. The order obtained in bacterial tests with rat liver S9 mix was more or less identical to that seen inthe tests with HepG2 cell homogenates but the concentrations of the aminesrequired to give positive results were in general substantially lower (10(-5)-10(-1) mu M). Overall, the results of the present study indicate that MN/HepG2 tests might reflect the mutagenic effects of HAAs more adequately than other in vitro mammalian cell systems due to the presence of enzymes involved in the metabolic conversion of the amines.

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Documento generato il 21/09/20 alle ore 18:02:14