enng and 2-anthramine

The aim of this work is to evaluate vitamins B antimutagenic effect against alkylatings methyl-N-nitro-N-nitrosoguanidine (MNNG), ethyl-N-nitro-N'- nitrosoguanidine (ENNG), frameshift mutagens 2-aminoanthracene (2AA) and 2-acetyl-amino-fluorene (2AF) and ROS-generating antibiotics norfloxacin (NOR) and nalidixic acid (NLX), using the in vitro Ames test. In vivo antimutagenesis studies were performed against urinary mutagens induced by NOR (70 mg/kg) or NLX (100 mg/kg) in CD1 mice. Vitamin B1 was antimutagenic against alkylatings MNNG (P<0.05) or ENNG (P<0.001). In fact as per the results observed during the current study, none of the vitamins reduced mutagenesis caused by frameshift mutagens. All of them reduced mutagenesis of NOR or NLX (P<0.001). In vivo studies showed that vitamins B1 and B6 (10 or 100 mg/kg) reduced urinary mutagens from NOR (P<0.001) or NLX (P<0.02) either free or β-glucoronidase-conjugates. None of the studied samples were toxic for the employed antimutagenic system. Vitamin B12 (4 mg/kg) reduced urinary mutagens of NOR or NLX (P<0.02). Vitamins B inhibited DNA mutations induced by ROS generated by NLX or NOR, both in vitro and in vivo. Vitamin B1is antimutagenic against mutations induced by the alkylating MNNG or ENNG. Based on the observations, employment of vitamins B in vivo can be a promising alternative to reduce genotoxic risk exposure to ROS.

Topics: 2-Acetylaminofluorene; Animals; Anthracenes; Antimutagenic Agents; DNA Damage; Methylnitronitrosoguanidine; Mice; Mice, Inbred Strains; Mutagenicity Tests; Mutagens; Mutation; Norfloxacin; Salmonella typhimurium; Thiamine; Vitamin B 12; Vitamin B 6

Magnolol, a component of the bark of Magnolia obovata, has been reported to possess various biological activities, such as anti-carcinogenicity, anti-promotion activity and anti-oxidative activity. These findings suggest potential for this compound in cancer chemoprevention. Interestingly, there have been no reports to date on the potential anti-mutagenic activity of magnolol, involving inhibition of initiation processes of the primary stage of carcinogenicity. In this study, anti-mutagenic activity of magnolol against mutagenicity induced by direct mutagens [1-nitropyrene (1-NP), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)] and indirect mutagens [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), benzo(a)pyrene (B(a)P), 2-aminoanthracene (2-AA) and 7,12-dimethylbenz[a]anthracene (DMBA)] were investigated using the bacterial mutagenicity test (Ames test). Results show that magnolol strongly inhibits mutagenicity induced by indirect mutagens, but does not affect direct mutagens. To elucidate the mechanism of this effect against indirect mutagens, effect of magnolol on CYP1A1- and CYP1A2-related enzyme activities of ethoxyresorufin-O-deethylase (EROD) and methoxyresorufin-O-demethylase (MROD) were investigated. Magnolol strongly and competitively suppressed these enzyme activities, suggesting it inhibited mutation induced by indirect mutagens through suppression of CYP1A1 and CYP1A2 activity.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Antimutagenic Agents; Benzo(a)pyrene; Biphenyl Compounds; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Imidazoles; Kinetics; Lignans; Male; Methylnitronitrosoguanidine; Microsomes, Liver; Molecular Structure; Mutagenicity Tests; Mutagens; Oxidoreductases; Quinoxalines; Rats; Rats, Sprague-Dawley; Salmonella typhimurium

The mutational specificities of various chemical mutagens were compared in isogenic E. coli strains with different DNA repair capabilities (wild-type, uvrA, umuC, and uvrA umuC) in a reversion assay employing a set of mutant lacZ genes that can detect two types of transitions, four types of transversions, and five kinds of specific frameshift events. A uvrA derivative was more sensitive than the wild-type strain to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone for +1G, -1G, -2(C-G), +1A and -1A frameshifts, G.C-->A.T transitions, and G.C-->T.A transversions. In a uvrA background, G.C-->T.A transversions and +1G, +1A, and -1A frameshifts appeared to be umuC-dependent, while G.C-->A.T transitions were not. N-Ethyl-N'-nitro-N-nitrosoguanidine was more mutagenic in a uvrA background for five kinds of frameshifts and G.C-->A.T transitions, but not for G.C-->T.A, A.T-->C.G, and A.T-->G.C base substitutions. A.T-->C.G transversions were totally dependent on umuC gene function. For the investigation of mutational specificities induced by frameshift mutagens, an rfa mutation was additionally introduced. The rfa strain responded to 2-nitrofluorene, which induced primarily -2(C-G) frameshift mutations. In an rfa uvrA background, benzo[a]pyrene induced +1G, -1G, +1A, and -1A frameshifts. 2-Aminoanthracene induced +1G, -1G, and +1A, but not -1A, frameshifts, with -1G frameshifts predominating. Ethidium bromide induced only two types of frameshifts, -1G and +1A. Frameshifts induced by ICR-170 were independent of umuC gene function, while those by induced 1-nitropyrene were partly umuC-dependent.

Topics: Adenosine Triphosphatases; Aminoacridines; Anthracenes; Bacterial Proteins; Benzo(a)pyrene; beta-Galactosidase; DNA Ligases; DNA Repair; DNA-Binding Proteins; DNA-Directed DNA Polymerase; Escherichia coli; Escherichia coli Proteins; Ethidium; Fluorenes; Frameshift Mutation; Furans; Genes, Bacterial; Glycosyltransferases; Lac Operon; Methotrexate; Methylnitronitrosoguanidine; Mutagenesis; Mutagenicity Tests; Mutagens; Nitrogen Mustard Compounds; Point Mutation; Pyrenes; Species Specificity; Suppression, Genetic