Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00249 (Mutagen)
 5,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutagen-induced intergenic and interallelic recombination as well as forward mutation were studied in one and the same strain of S. cerevisiae. In nontoxic dose ranges, the induction of mutants and recombinants was parallel after treatment with ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), N-methyl-N'-nitro-M-nitrosoguanidine (MNNG), triethylene melamine (TEM), 4-nitroquinoline 1-oxide (4-NQO), sodium nitrite (NaNO2), and 1-fluoro-2,4-dinitrobenzene (2,4-DNFB). Acridine orange (AO) after treatment without light induced recombinants, but reduced the frequency of spontaneous mutations. In combination with TEM, AO exerted the same effect, i.e., reduced its mutagenic effect and enhanced its recombinogenic effect. 4,5,6-Trichloro-2-(2,4-dichlorophenoxy) phenol (Cl5-predioxin) induced mutants and intergenic recombinants, but specifically reduced the spontaneous frequency of interallelic recombinants. In combination with TEM, it enhanced its mutagenic and intergenic recombinogenic effects but reduced its interallelic recombinogenic effect. The main conclusions of the present study, that is 1. Essentially similar lesions can lead to different genetic consequences, and 2. Induction of mutation and recombination are jointly correlated, i.e., suppression of mutations leads to an enhancement of recombinations, while suppression of recombinations leads to an enhancement of mutations, are used to set up a speculative concept for mutation and recombination induction in the diploid yeast cell during mitosis.
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PMID:Evidence that induction and suppression of mutations and recombinations by chemical mutagens in S. cerevisiae during mitosis are jointly correlated. 10 36

Drosophila melanogaster males from a Basc stock were mutagenized with either X-rays, ethyl methanesulfonate (EMS), or nitrogen mustard (HN2). Groups of identically treated males were crossed to different types of female. Sex-linked recessive lethals were scored as a genetic end point. The females used were homozygous for X-chromosomal mutations (mus(1)101D1, mus(1)104D1, mei-9 or mei-41D5) which lead to defective DNA repair and which increase the mutagen sensitivity of larvae. Females from a white stock with normal DNA repair capacities served as controls. The premutational lesions induced in mature sperm are only processed after insemination by the maternal enzyme systems present in the oocytes. Differences in the efficiency of the processing of lesions can lead to maternal effects on the frequency of mutations recovered from mutagenized sperm. It was found that, with the exception of mus(1)104D1, all mutants analysed significantly modify the mutation fixation of one or more types of premutational lesions. The most drastic effect is found with the mus(1)101D1 stock in which HN2-induced DNA cross-links do not lead to sex-linked recessive lethals. It is assumed that mus(1)101D1 is defective in an early step of DNA cross-link repair. Our first set of data clearly demonstrates that the study of maternal effects in Drosophila is an efficient tool to analyse the in vivo function of repair mutations on chemically induced mutagenesis.
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PMID:Mutagen-sensitive mutants in Drosophila melanogaster: effects on premutational damage. 11 70

The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays.
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PMID:Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP. 19 23

Invertase formation in the yeast Saccharomyces cerevisiae is subject to repression by hexoses in the growth medium. Mutagen-induced (ethyl methanesulfonate or N-methyl-N-nitro-nitrosoguanidine) invertase hyperproducer mutants have been derived from the SUC3 MAL3 strain EK-6B by selecting for their ability to grow on media containing the sugar raffinose plus 2-deoxy-D-glucose (2DG). Raffinose like sucrose is a betta-fructoside which can be hydrolyzed by yeast invertase (beta-fructoside which can be hydrolyzed by yeast invertase (beta-fructofuranoside fructohydrolase). These mutants, designated dgr, produce higher levels of invertase (pi-glucosidase levels are also elevated but to a lesser extent) under conditions normally repressing invertase biosynthesis in the parent. Invertases of mutants dgr2 and dgr3 are indistinguishable from that of EK-6B with respect to their Km's for sucrose and thermal labilities. Genetic studies revealed that dgr2 and dgr3 are recessive and unlinked to the SUC3 gene.
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PMID:Genetic control of invertase formation in Saccharomyces cerevisiae. II. Isolation and characterization of mutants conferring invertase hyperproduction in strain EK-6B carrying the SUC3 gene. 36 57

Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant mutant types and to some actual problems of induced mutagenesis.
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PMID:Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis. 36 69

Induction of 8-azaguanine-resistant mutation, DNA single-strand breaks, and chromosome aberrations by treatment with ethyl methanesulfonate (EMS), N-methyl-N'nitro-N-nitrosoguanidine (MNNG), nitrogen mustard hydrochloride (HN2), or 4-nitroquinoline 1-oxide (4-NQO) was compared under similar experimental conditions using cultured FM3A cells from a C3H mouse mammary carcinoma. All the chemicals induced 8-azaguanine-resistant mutations and chromosome aberrations in a dose-dependent manner; a good correlation between the two activities was demonstrated. An alkaline sucrose gradient method demonstrated that DNA single-strand breaks were induced only in a high dose range by 1- and 24-hr treatment with the chemicals. One exception was that a 1-hr treatment with HN2 produced an anomalous sedimentation pattern. These data suggest that caution is necessary for the interpretation of results obtained by the alkaline sucrose gradient analysis, and that examination of mutagenicity and chromosome aberrations is more feasible as screening procedures for potential mutagens than analysis of DNA single-strand breaks.
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PMID:Comparison of mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations in cultured mouse cells by potent mutagens. 41 23

The effects of altering glutathione (GSH) levels in the male reproductive tract have been studied in an attempt to establish a link between chemical-induced perturbations in glutathione and susceptibility of spermatozoa to chemical insult. Tissue GSH levels were enhanced by a treatment regimen of N-acetylcysteine (NAC) (250 mg/kg, 4 treatments at 2 h intervals). With this treatment, GSH levels in liver, testis, caput epididymis, and cauda epididymis were elevated to 126%, 110%, 178%, and 136% of control values. Sexually mature male rats were then treated with NAC and challenged with a dose of EMS (100 mg/kg) to determine if enhanced tissue GSH would protect against EMS-induced dominant lethal mutations. Pretreatment with NAC significantly decreased the post-implantation loss from 7.05 +/- 0.57 with EMS alone to 5.28 +/- 0.47. Conversely, a dominant lethal assay was conducted using different doses of phorone pretreatment to determine the relative contribution of hepatic versus reproductive tract GSH in protecting against EMS-induced dominant lethal resorptions. Doses of 100 mg/kg and 250 mg/kg phorone significantly lowered both hepatic and reproductive tract GSH while 25 mg/kg lowered only hepatic GSH. These three dose levels were used as pretreatments in a dominant lethal study followed by a challenge administration of EMS (50 mg/kg), which is a threshold dose of EMS for producing dominant lethal mutations. Comparison against controls demonstrated a significant potentiation of fetal resorptions in all groups receiving phorone pretreatment, including the 25 mg/kg pretreatment group which only lowered hepatic GSH prior to EMS challenge. The results of these experiments indicate that GSH reserves in the male reproductive tract are insufficient to protect developing spermatozoa from damage by alkylating agents in the absence of hepatic GSH.
Teratog Carcinog Mutagen 1992
PMID:Effects of reproductive tract glutathione enhancement and depletion on ethyl methanesulfonate-induced dominant lethal mutations in Sprague-Dawley rats. 135 63

Mutagen-sensitive (mus) mutations in Drosophila melanogaster render developing flies hypersensitive to the lethal effects of DNA-damaging agents. In principle, multiply mutant mus strains might then serve as sensitive in vivo indicators of a wide range of mutagens and genotoxic carcinogens. As a first step to evaluate that potential we characterized interactions between mus mutations in eight double mutants containing combinations of the second chromosomal mutations mus201D1, mus205B1, mus208B1, mus210B1 and mus211B1. We found that (i) all double mutants are fully viable in the absence of mutagen exposure, (ii) mus205B1 is epistatic to any other mus mutation with respect to methyl methanesulfonate (MMS) sensitivity, and (iii) in double mutants carrying any combination of mus201D1, mus210B1 or mus211B1, MMS sensitivity is increased in a synergistic manner. Based on those results, and on mutagen cross-sensitivity data of single mutants generated in previous studies, we constructed two triple mutant mus strains for use as testers in a simple genotoxicity assay. That assay measures the survival of DNA repair-deficient mus homozygotes relative to their repair-proficient heterozygous siblings. Those two classes of fly are easily distinguished from one another by their phenotypic markers. In addition, the heterozygotes serve as a relatively mutagen-insensitive internal control in all test vials. One tester strain (mus208B1 mus210B1 mus211B2) identified 11 of 12 chemical carcinogens as genotoxic (benzo[a]pyrene, cyclophosphamide, 1,2,3,4-diepoxybutane, diethylnitrosamine, dimethylnitrosamine, ethyl methanesulfonate, formaldehyde, hexamethylphosphoramide, methyl methanesulfonate, methylnitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine). Safrole and two noncarcinogens (benzo[e]pyrene and caprolactam) tested as nongenotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A rapid somatic genotoxicity assay in Drosophila melanogaster using multiple mutant mutagen-sensitive (mus) strains. 147 14

In this work we report on the isolation of an Escherichia coli K-12 mutation, which confers a high sensitivity to bacteria cells to mutagenesis by simple monofunctional alkylating agents. The mutation emerged spontaneously from a bacterial strain that already proved useful in various mutagenicity studies. By monitoring the influence of such a mutation on the frequency of induced mutation by ethylating (EMS, DES, ENU, ENNG) vs. methylating (MMS, DMS, MNU, MNNG) compounds, and on the in vivo repair capacity for different alkyl-DNA lesions (O6-alkG, N7-alkG, N3-meA), we conclude that the mutation should affect the gene (ogt) that encodes constitutive DNA repair alkyltransferase (ATase). Thus in the presence of ada, differences in mutagenicity were observed only with ethylating agents; the sensitization of cells to both the ethylating and methylating partners requiring, by contrast, the absence of the ada protein. These results support the reported in vitro substrate specificities for both ogt and ada ATases. The parental cells exhibited biphasic dose-response curves in accordance with the idea of low basal level saturation attributed to the uninducible ogt ATase. Deficient bacterial derivatives showed, by contrast, linear mutation induction responses. The in vivo removal of alkylated bases from DNA was measured in bacterial strains deficient in the excision repair pathway (delta uvrB) and unable to induce the adaptive response (ada::Tn10). The very low initial levels for O6-meG and O6-etG (1.1 and 0.2 molecules per cell, respectively) were readily repaired by the parental cells but remained unchanged in the hypermutable derivatives. This result suggests that in the absence of nucleotide excision repair and of the adaptive response, no alternative pathway, other than ogt, is available for the repair of the major mutagenic lesion, O6-alkG, at least during the first 4 hours after alkylation. Comparatively, no differences were found in the capacity to repair the major lethal adduct, N3-meA, in agreement with the fact that no effect on cell survival was detected. In conclusion, we propose that the biological significance of the ogt protein relies mainly on its ability to prevent mutagenesis by low levels of bulkier ethylation products (especially in the absence of uvr excision repair.(ABSTRACT TRUNCATED AT 400 WORDS)
Environ Mol Mutagen 1992
PMID:Mutagenesis and DNA repair for alkylation damages in Escherichia coli K-12. 160 Sep 55

The genotoxicity of the terpene beta-myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 micrograms/ml (limit of solubility) in the presence and absence of S9-mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt-locus in V79-cells. Tests with and without S9-mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE-inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79-cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of premutagens and precarcinogenes is discussed.
Environ Mol Mutagen 1991
PMID:Evaluation of the mutagenicity of beta-myrcene in mammalian cells in vitro. 186 66


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