bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the H2O2‐induced SOS response in escherichia coli PQ300 by amino acids, metal chelators, antioxidants, and scavengers of reactive oxygen species
Authors: Müller Jürgen , Janz Siegfried 
Published: February 2007

AbstractThe SOS chromotest is a simple colorimetric genotoxicity assay that monitors DNA repair by measuring the induction of the gene sfiA in Escherichia coli K‐12. E. coli PQ300, a diagnostic SOS tester strain for the detection of oxidative genotoxins, carries a mutation in a key gene for antioxidative defense, oxyR. This mutation renders PQ300 more sensitive to oxidative genotoxins, particularly to H2O2. We found that induction of the SOS response by H2O2 in E. coli PQ300 is dependent on the composition of the incubation medium; a substantially reduced response was obtained in minimal phosphate buffered saline (PBS) as opposed to complex Luria broth (LB) medium. Supplementation of PBS with histidine or cysteine stimulated H2O2‐induced SOS induction to levels exceeding those found in LB medium. Low concentrations of glutathione (20–70 μM) also enhanced the H2O2‐induced SOS response in E. coli PQ300, whereas higher concentrations (>150 μM) were protective. Preincubation of tester cells with the chelators o‐phenanthroline, 2,2‐dipyridyl, and ethylenediaminetetraacetic acid (EDTA) protected cells from the effects of H2O2, although EDTA was only partially effective. Pretreatment of PQ300 with the antioxidant ascorbic acid or the hydroxyl radical scavenger dimethyl sulfoxide also diminished the SOS response, whereas mannitol and glucose were ineffective. The results show that the net effect of H2O2‐induced DNA damage is influenced by the balance of oxidative and antioxidative factors and, furthermore, can be modulated by constituents of the extracellular milieu. © 1993 Wiley‐Liss, Inc.
Screening of Azo dyes for mutagenicity with ames/salmonella assay
Authors: Kaur Anupam , Sandhu R. S. , Grover I. S. 
Published: February 2007

AbstractAzo dyes, the largest portion of manufactured dyestuffs, are primarily used as colouring substances in food, textiles, and the plastic industry. It has been estimated that 128 tonnes per annum of dyes are released into the environment worldwide [Anliker, 1977]. Certain azo compounds are known to be mutagenic in bacterial tests [Yahagi et al., 1975; Venitt and Bushell, 1976; Brown et al., 1978]. Watersoluble dyes are biotransformed by intestinal micro‐organisms in the gastro intestinal tract, and the toxicity, mutagenicity, and carcinogenicity of these dyes in the gut or liver may be attributed to their metabolites. Since it is desirable to have a genotoxic evaluation of a chemical being released into the environment in order to check their indiscriminate use, a project has been initiated to determine the mutagenicity of the azo dyes being used commercially. The present report deals with the results of 13 dyes tested in Salmonella typhimurium with and without metabolic activation. © 1993 Wiley‐Liss, Inc.
G2 chromatid aberrations: Kinetics and possible mechanisms
Authors: Bryant Peter E. , Slijepcevic Predrag 
Published: February 2007

AbstractChromatid breaks and exchanges are induced by radiation in G2 mammalian cells. Breaks are at a maximum number at about 30 min after irradiation and decrease apparently exponentially with time between irradiation and sampling. Few breaks are observed immediately following exposure, probably as a result of selection of mitotic cells where chromosomes are condensed and there is consequently a lack of time for expression of damage. The change in frequency of breaks with time, from 30 min after radiation exposure and onwards, can be interpreted in two possible ways: either in terms of a repair process or in terms of a change in radiosensitivity through G2. However, our results with an inhibitor of repair of DNA double‐strand breaks (ara A) and with “transient hypothermia” which extends the G2 phase, argue for an interpretation based on rejoining of chromatid breaks, possibly reflecting the repair of a subclass of dsb. Data from experiments with irradiated and restriction endonuclease treated radiosensitive mutant rodent lines indicate that enhanced levels of conversion of dsb into chromosomal aberrations may be largely independent of repair rates of bulk dsb. In CHO cells and in human lymphocytes exchanges initially increase rapidly with time and then remain at a constant frequency, supporting the notion of a uniform chromosomal radiosensitivity throughout most of G2 and providing further evidence that the mechanism for mis‐joining broken chromatids (leading to exchanges) is different from that for rejoining of chromatid breaks. Ratios of breaks to exchanges were found to vary in different cell lines and at different times during treatment with inhibitors or at altered temperatures, possibly (in different cell lines) indicating different levels of enzymes involved in misjoining, but suggesting that the mechanisms of chromosomal rejoining and misjoining are independent, at least to some degree. © 1993 Wiley‐Liss, Inc.
Molecular mechanisms for the induction of chromosomal aberrations in CHO cells heated in S phase
Authors: Wong Rosemary S. L. , Dewey William C. 
Published: February 2007

AbstractChromosomal aberrations are induced by heat only when Chinese hamster ovary cells are heated in S phase of the cell cycle. Studies on the hyperthermic inhibition of cellular DNA replication have indicated that four molecular aspects of DNA replication are affected after heating. New replicon initiation and DNA chain elongation are inhibited; the fork displacement rate is very sensitive to heat‐inactivation; and finally, there is almost a two‐fold increase in single‐stranded regions in the replicating DNA after heating. From a comparison of these altered processes between S phase cells and heated G1 cells, which do not die from chromosomal aberrations, our current hypothesis involves 3 steps for the chromosomal aberration induction process. The first critical step is the persistent increase of single‐stranded regions in the replicating DNA. Then, we hypothesize that the second step is the creation of transient double strand breaks (DSBs) induced at sites opposite these regions by endogenous endonucleases. Finally, the third step requires that improper repair of these DSBs occurs from either nonrepair or misrepair which then leads to the final chromosomal aberrations seen in the first mitosis after treatment. We believe that this 3 step induction process is common for any cytotoxic agent that induces chromosomal aberrations after DNA replication has been inhibited. © 1993 Wiley‐Liss, Inc.
Mechanism of induction of chromosomal aberrations by inhibitors of DNA topoisomerases
Authors: Palitti F. 
Published: February 2007

AbstractEvidence is provided that antitopoisomerase drugs induce chromosomal aberrations via the formation of DNA double strand breaks. Camptothecin, an inhibitor of DNA topoisomerase I, produced only chromatid‐type aberrations, and in order to be effective it has to be present during the DNA replication. The fact that it induces chromosomal aberrations also in the G2 phase of the cell cycle suggests the presence of a residual DNA synthesis in this phase. A pretreatment with aphidicolin, an inhibitor of DNA polymerases, reduces the camptothecin induced aberrations in the G2 phase, confirming the need of DNA synthesis for the induction of aberrations by the inhibitor of DNA topoisomerase I. © 1993 Wiley‐Liss, Inc.
Detection of opiate‐enhanced increases in DNA damage, HPRT mutants, and the mutation frequency in human HUT‐78 cells
Authors: Shafer David A. , Xie Yiping , Falek Arthur 
Published: February 2007

AbstractIn previous studies we have shown highly significant increases in chromosome damage and sister chromatid exchanges in heroin addicts, particularly when caffeine and metabolic inhibitors are added to the medium. Using human HUT‐78 T‐cell cultures, we now find direct in vitro evidence of opiate‐induced or opiate‐promoted mutagenesis via several assay systems. First, with microgel electrophoresis (MGE), we observed graded, dose‐dependent, significant increases (P < .0001) in the frequency of comet tails of fragmented DNA when cells were treated with morphine alone (5 × 10−9M up to 10−7M) or when co‐treated with the more potent mutagen, ethylmethanesulfonate (EMS). There were also dose‐dependent increases in the lengths and densities of the comet tails observed. These findings were confirmed by a series of MGE experiments in which several days of morphine exposure preceded a 2‐hr pulse of EMS. Second, mutant frequency (MF) assays also indicated significant opiate effects. These studies required separate assessment of cloning efficiencies and the frequencies of TG‐resistant, HPRT‐deficient mutant clones under four test conditions: no treatment, morphine alone for 4 days, morphine plus EMS, and EMS alone. Prior to the treatment phase, aminopterin was used to eliminate background HPRT mutations. The medium was changed after the treatment phase, the cells were allowed to express mutant pheno‐types, and then TG was added and resistant mutant clones counted after 16 days. The background MF level for controls and for cells treated with EMS alone were negligible at 5.12 × 10−8 and 7.25 × 10−8, respectively. In the cells treated with morphine alone or morphine plus EMS, MF levels increased very significantly (P < .001) by >100‐fold to 5.1 × 10−6 and 7.0 × 10−6, respectively. Cloning efficiency also decreased significantly with both morphine‐exposed conditions. Preliminary analysis with the single strand conformational polymorphism (SSCP) procedure following 6‐thioguanine (TG) selection, also confirmed the occurrence of Exon 3 mutants of the HPRT gene in cells exposed to morphine plus EMS. It appears that brief EMS exposure can be repaired, whereas, if morphine exposure persists through one or more cell cycles, direct or indirect mutagenesis is initiated. © 1994 Wiley‐Liss, Inc.
Comparative mutagenicity of plant‐activated aromatic amines using salmonella strains with different acetyltransferase activities
Authors: Wagner Elizabeth D. , Smith Shannon R. , Xin Hua , Plewa Michael J. 
Published: February 2007

AbstractPlant systems can activate aromatic amines into mutagens. In the plant cell/microbe coincubation assay, we earlier demonstrated that 2‐aminofluorene and m‐phenylenediamine were activated by plant cells into mutagens with reversion at the hisD3052 allele in Salmonella typhimurium strain TA98 as the genetic endpoint. New derivatives have been developed which possess elevated levels of acetyl‐CoA:N‐hydroxyarylamine O‐acetyltransferase which are very sensitive to N‐hydroxylated amines [Watanabe et al., 1990: Mutat Res 234:337‐348]. The objectives of this research were to examine Salmonella strains with different acetyltransferase activities in the plant cell/microbe coincubation assay with a series of structurally related aromatic amines. The hypothesis tested was whether and to what degree a plant‐activated metabolite of these aromatic amines could serve as a substrate for bacterial O‐acetyltransferase and induce mutation in Salmonella. Every aromatic amine examined was activated by plant cells with YG1024 (the strain with elevated O‐acetyltransferase activity) as the genetic indicator organism. The rank order of the mutagenic responses of YG1024 to the plant‐activated aromatic amines was 2‐aminofluorene >benzidine > m‐phenylenediamine > 4‐aminobiphenyl > 2,4‐diaminotoluene > 2‐naphthylamine. This rank order was expressed by TA98 but to a much lower degree. There was a very slight mutagenic response observed in TA98/1,8‐DNP6 (a strain lacking O‐acetyltransferase activity) with the plant‐activated metabolites of benzidine and 4‐aminobiphenyl. We conclude that the plant‐activated aromatic amines are substrates for bacterial O‐acetyltransferases. © 1994 Wiley‐Liss, Inc.
Assay by inhibition of repair to measure O6‐methylguanine in DNA
Authors: Mironov Nikolai M. , Martel‐Planche Ghyslaine , Wild Christopher P. 
Published: February 2007

AbstractA procedure for measuring the level of O6‐me‐thylguanine (O6‐meG) in DNA is described. Repair of 32P‐oligodeoxynucleotides containing O6‐meG adducts by O6‐alkylguanine alkyltransferase (AGT) was performed in the presence of different quantities of DNA containing unknown concentrations of O6‐meG. Each methylated DNA sample inhibited the repair of oli‐godeoxynucleotide substrate to an extent dependent upon O6‐meG concentration. Each DNA sample tested at different concentrations in the assay therefore had a characteristic inhibition curve and could be compared to the curves generated using reference DNA samples of known O6‐meG concentration. We report the method of calculation of the O6‐meG level in a given DNA sample by comparison of its inhibition curve with that of reference DNAs. This method of calculation does not require a knowledge of the exact quantity of the labelled substrate or AGT used. The method requires only 0.1‐10 μg of DNA, with a limit of detection of 0.8 fmol of O6‐meG per μg of DNA. © 1994 Wiley‐Liss, Inc.
Studies on cytotoxic and genotoxic effects of cadmium nitrate and lead nitrate in chinese hamster ovary cells
Authors: Lin Ruey H. , Lee Ching H. , Chen Wen K. , Lin‐Shiau Shoei Y. 
Published: February 2007

AbstractCadmium nitrate decreased the viability of Chinese hamster ovary (CHO) cells in a concentration‐dependent manner; 50% inhibition (IC50) was achieved at 0.015 mM. In contrast, lead nitrate appeared to be less toxic. Neither cadmium nitrate nor lead nitrate significantly increased frequencies of binucleated CHO cells with micronuclei (MN). However, both cadmium nitrate and lead nitrate could augment sister chromatid exchanges (SCEs). Cadmium nitrate induced SCEs with a potency approximately equal to that of mitomycin C and more than 10 times higher than lead nitrate. Cadmium nitrate also increased chromosome aberrations (CAs), which included breaks, acentrics, interchanges, and dicentrics of chromosomes. In addition, cadmium nitrate induced a decrease in the mitotic index (MI), but lead nitrate increased it. In summary, it appears that both of these two heavy metal salts have cytogenetic toxicities with different degrees of effects on the cytotoxicity, MN, CAs, and SCEs in CHO cells. However, SCE was the most sensitive endpoint for indicating mutagenetic effects of cadmium and lead in the present study.
Evaluation of the genetic toxicity of middle distillate fuels
Authors: McKee R. H. , Amoruso M. A. , Freeman J. J. , Przygoda R. T. 
Published: February 2007

AbstractPetroleum middle distillate (PMD) fuels are mixtures of hydrocarbons that distill between ∼ 170‐370°C. Commercial products that fall into this category include kerosine, diesel fuel, jet fuel, and home heating oil. These products contain both saturated (paraffins and cycloparaffins) and aromatic species, but because of the boiling range normally contain very small amounts of the 3‐6 ring polycyclic aromatic hydrocarbon (PAH) constituents, which are considered to be carcinogenic. Nevertheless, there is evidence of weak tumorigenic activity when these materials are repeatedly applied to mouse skin.In the current studies representative products were tested in two commonly used, short‐term assays for genetic toxicity, the Salmonella/mammalian microsome mutagenicity assay and the mouse bone marrow micronucleus test. All samples were inactive in the micronucleus assay, and three were clearly inactive in the Salmonella test. Of the remaining two, one was marginally active in the Salmonella assay, and one was equivocal. The marginally active sample contained detectable levels of PAH due to the use of catalytically cracked materials as blending stocks. The results indicated that PMDs that do not contain cracked material were not mutagenic. Thus they may produce tumors via nongenotoxic processes. Those products that do contain cracked stocks may have sufficient PAH to be mutagenic in the Salmonella assay, and in those cases the PAH might also contribute to tumor formation. © 1994 Wiley‐Liss, Inc.
Mutability of salmonella tester strains TA1538 (hisD3052) and TA1535 (hisG46) containing the UmuD' and UmuC proteins of escherichia coli
Authors: Urios Amparo , Herrera Guadalupe , Aleixandre Vicente , Sommer Suzanne , Blanco Manuel 
Published: February 2007

AbstractWe have studied the mutability of Salmonella typhimurium tester strains carrying plasmids in which either the umuDC or the umuD'C operon of Escherichia coli have been cloned. Reversion of the hisD3052 frameshift mutation by benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1) and 1‐nitropyrene (1‐NP), was very efficiently promoted by UmuD' (the activated form of UmuD) and UmuC proteins. In contrast, UmuD'C proteins promoted a moderate reversion of the missense hisG46 allele by B[a]P, and were not effective in mediating this reversion by AFB1. The Salmonella tester strain carrying the hisD3052 allele and containing the E. coli UmuD'C proteins has a sensitivity toward frameshift mutagens similar to that of the MucAB containing strain TA98, and may be useful for obtaining a high level of mutants generated by the SOS mutagenic mechanism in the absence of MucAB proteins. © 1994 Wiley‐Liss, Inc.
Mutagenicity testing in Salmonella typhimurium strains possessing both the his reversion and ara forward mutation systems and different levels of classical nitroreductase or O‐acetyltransferase activities
Authors: Jurado Juan , Alejandre‐Durán Encarnación , Pueyo Carmen 
Published: February 2007

AbstractThe induction of forward mutations to L‐arabinose resistance (AraR) and of reversions to histidine prototrophy (His+) can be quantitatively compared in Salmonella typhimurium BA strains. The BA bacteria carry the araD531 allele required for the Ara assay and a his auxotrophy (hisD3052 or hisG46) required for the His assay. In this study, 2 new sets of BA indicator strains have been constructed in order to combine the Ara forward and the His reverse mutation assays of S. typhimurium with deficiency, or overproduction, in either classical nitroreductase or O‐acetyltransferase for mutagenicity testing of nitro‐containing chemicals. Nine mutagens with different chemical structures were tested to compare the specific mutagenic sensitivities of the new constructions with those of the parental and of the conventional TA indicator bacteria. The Ara test, which responded with high sensitivity to all chemicals tested, revealed important differences between the standard tester strains TA98 and TA100 with respect to the activation of mutagens considered to be dependent on classical nitroreductase activity. Total correspondence was found between the specific mutagenic sensitivities of the defective and the overproducing bacteria in the genetic background of TA98 but not in that of TA100. In the genetic background of TA100, chemicals such as nitrofurantoin and nitrofurazone displayed 10‐fold reduced mutagenicity to the “classical nitroreductase” defective strain without increasing mutagenicity to the corresponding overproducing bacteria. This discrepancy might be attributed to the greater nitroreduction capability of strain TA100 (68.12 nmole/min/mg protein) as compared to TA98 (24.42 nmole/min/mg protein), by assuming that nitrofurantoin and nitrofurazone are such good substrates for classical nitroreductase that the additional enzyme activity produced from the corresponding overexpressing plasmid when present in TA100 no longer affected their metabolic activation. We propose that the Ara forward mutation test carried out in the set of overproducing bacteria constructed in the genetic background of TA98 might play a role for routine testing of large number of samples. The isogenic defective strains could be used in cases of uncertain results with the corresponding overproducing bacteria. Finally, the reversion of the his alleles accompanying the Ara assay in the BA strains could play a role in assessing the presence of mixtures of chemicals with different mutagenic specificity in samples of environmental relevance such as urban air, foods, and water.
Types of chromosomal aberrations induced by seed aging in crepis capillaris
Authors: Dimitrov Boyan D. 
Published: February 2007

AbstractThe types of chromosomal aberrations during the aging of Crepis capillaris (Hawksbeard; fam. Asteraceae) seeds were investigated. Seeds were stored at 22°C for 2, 4, 6, and 8 years. Chromosomal aberrations were analyzed in metaphase chromosomes at the first and second mitotic cycles. A colchicine block was used for the differentiation of individual mitotic cycles. The frequency of chromosomal aberrations induced during seed aging gradually increased with the increase in the time of aging, reaching its maximal value after 8 years of aging. Both chromatid and chromosome types of aberrations were observed in first mitosis. At all times of aging, the frequency of chromosome‐type aberrations considerably surpassed the frequency of the chromatid type. At the different times of aging, the frequency of chromosome‐type aberrations was 3–4.5 times higher than that of chromatid‐type aberrations. In the second mitosis, the frequency of both aberration types was low. The frequency and type of derived chromosomal aberrations observed in second mitosis corresponded to those observed in first mitosis. These results are discussed in relation to the factors inducing chromosome lesions during seed aging and the mechanism of formation of chromosomal aberrations. © 1994 Wiley‐Liss, Inc.
mutation spectra of Glu‐P‐1 in Salmonella: Induction of hotspot frameshifts and site‐specific base substitutions
Authors: Levine Jessie G. , Knasmüller Siegfried , Shelton Melissa L. , Demarini David M. 
Published: February 2007

AbstractWe used colony probe hybridization and PCR/ DNA sequence analysis to determine the mutations in —1,640 revertants of the ‐1 frameshift allele hisD3052 and ‐260 revertants of the base substitution allele hisG46 of Salmonella typhimurium induced by the heterocyclic amine cooked food mutagen 2‐amino‐6‐methyldipy‐rido[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐1). All of the mutations were at sites containing guanine, which is the base at which Glu‐P‐1 forms DNA adducts. A hotspot mutation involving the deletion of a CG or GC within the sequence CGCGCGCG accounted for 100% of the Glu‐P‐1‐induced mutations at the frameshift allele in strains TA1978 (uvr+) and TA1538 (uvrB) and 99% in TA98 (uvrB, pKM101). To explain the induction of these hotspot mutations by Glu‐P‐1, we describe here a more detailed version of our recently proposed correct incorporation/ slippage model [Genetics:136:731, 1994]. We propose that after cytosine is incorporated correctly opposite a Glu‐P‐1‐adducted guanine, various slipped intermediates may form (a total of 18), depending on which guanine is adducted and whether it remains within the helix or becomes extrahelical. This variety of mutational pathways may account for the high mutability of the hotspot sequence by Glu‐P‐1. Although the pKM101 plasmid does not influence the mutagenic potency or mutational spectrum of Glu‐P‐1 at the frameshift allele, it is required by Glu‐P‐1 to revert the base substitution allele, where Glu‐P‐1 induces G‐C‐→T‐A transversions (75%) and G‐C→T.A transitions (25%) exclusively at a single site (the second position of the CCC codon of the hisG46 allele). The limited (20–30 times less) base substitution mutagenic potency of Glu‐P‐1 relative to its frameshift mutagenic potency as well as the extreme site specificity exhibited by Glu‐P‐1 for base substitutions may have bearing on the lack of base substitutions identified in ras genes in Glu‐P‐1‐induced rat colon tumors. © 1994 Wiley‐Liss, Inc.