• Toxicological Research
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• v.4 no.2
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• pp.131-142
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• 1988

The post-mitochondrial liver fractions (S-9) were prepared from rats and hamsters which have been treated with Aroclor 1254 (PCB) and the capacities of these S-9 fractions to generate mutagenic metabolites from several well known procarcinogens have been compared. Benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3-MC), Aflatoxin B1(AFB1), 2-acetylamino-fluorene(AAF), and 2-aminofluorene (AF) were employed as promutagens in the Salmonella reverse mutation tests. Results showed that the rat and hamster S-9 fractions had differential abilities to produce mutagenic metabolites from a given promutagen.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.93-94
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• 2001

Former studies dealing with combined effects caused by chemical compounds in the metabolically competent hepatoma cell line Hep G2 indicated that Hep G2 cells are useful and sensitive indicators for the identification of synergisms of promutagens, comutagens and antimutagens which are relevant in eukryontic (human) cells. In the present study we examined the modulation of DNA damages by the suspected antimutagens ascorbic acid, beta-carotene, alpha-naphthoflavone and beta-naphthoflavone in Hep G2 cells.(omitted)

• Environmental Mutagens and Carcinogens
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• v.23 no.3
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• pp.94-98
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• 2003

Quercetin and naringenin are representative flavonoids that not only exert anti estrogenic, cholesterol-lowering and antioxidant activities but also can modulate the metabolism of many xenobiotics. The activity of the specific form(s) of CYP450 is likely to be a major determinant of susceptibility to chemically induced carcinogenesis between which varies among between individuals due to different dietary habits as well as genetic characteristics. People consume cooked meat or fish together with various vegetables containing substantial amounts of quercetin and naringenin that can modify the enzyme activity of CYP1A2 to stimulate or to inhibit the mutagenic activities of HCAs. Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 mM, respectively, but suppressed 82% and 96% at 50 mM and 100 mM. Naringenin also increased the MeIQ-induced mutation about 37% and 22% at 0.1 and 1 mM, but suppressed it 32% and 63% at 50 mM and 100 mM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. Collectively, it is likely that the biphasic effects of quercetin and naringenin on the MeIQ-induced mutagenesis in S. typhimurium TA1538/CYP1A2bc-b5 were due to their differential modification of the CYP1A2 activity in these cells.