bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative relationship between ethylated DNA bases and gene mutation at two loci in CHO cells
Authors: Fortini P. , Calcagnile A. , di Muccio A. , Bignami M. , Dogliotti E. 
Published: February 2007

AbstractIn a previous study we showed that the formation of O6‐ethylguanine (O6‐EtGua) in the DNA of CHO cells in culture correlated with mutations induced by ethylnitrosourea (ENU) and diethylsulfate (DES) at the hypoxanthine‐guanine‐phosphoribosyltransferase (hprt) locus but not at the Na, K‐ATPase locus. This study was extended to another ethylating agent, ethyl methanesulfonate (EMS). DNA adduct formation and induction of mutation at the two gene loci were determined simultaneously in CHO cells after EMS exposure. The extent of ethylation at the N7 and O6 positions of guanine and at the N3 site of adenine were measured and the possible correlations with 6‐thioguanine resistance (6‐TGr) and ouabain resistance (ouar) mutations were investigated. A good correlation between the levels of ethylation at O6 guanine and mutation frequency at hprt gene by all three ethylating agents was observed. In the case of the ouar locus, the frequency of O6‐EtGua adducts correlated with mutation induction by EMS and ENU but not by DES. Although both EMS and DES have similar reaction mechanisms, these results highlight differences in their mutational specificity. The comparison of this type of analysis with mutational spectra revealed that correlation studies may be inadequate to analyse multi‐component phenomena like mutation formation. © 1993 Wiley‐Liss, Inc.
Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization
Authors: Camoirano A. , de Flora S. , Dahl T. A. 
Published: February 2007

AbstractReactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy‐transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy‐transfer and electron‐transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine‐xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair‐deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N‐acetyl‐L‐cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair‐deficient bacteria. Distance‐dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase. © 1993 Wiley‐Liss, Inc.
Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminium‐induced sister‐chromatid exchanges in mouse bone marrow
Authors: Dhir Haimanti , Roy Ajoy Kumar , Sharma Archana 
Published: February 2007

AbstractThe identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)‐induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract. ©1993 Wiley‐Liss, Inc.
Base‐pair mutations caused by six aliphatic epoxides in salmonella typhimurium TA100, TA104, TA4001, and TA4006
Authors: Einistö P. , Hooberman B. H. , Sinsheimer J. E. 
Published: February 2007

AbstractSalmonella typhimurium strains TA100, TA104, TA4001, and TA4006 were used to detect the base‐pair mutations caused by six aliphatic epoxides: chloropropylene oxide, glycidyl 1‐naphthyl ether, glycidyl 4‐nitrophenyl ether, 1‐naphthyl‐propylene oxide, styrene oxide, and trichloropropylene oxide. Dose‐mutagenicity relationships could be established for all six epoxides in strains TA100 and TA104 but not in strains TA4001 and TA4006. These results, together with the lack of sensitivity of the TA100 revertants to DL‐1,2,4‐triazole‐3‐alanine, indicate CG→TA transitions and/or CG→AT transversions are of major importance for mutations induced by these epoxides in Salmonella TA100 and possibly TA104. In addition, since the reproducibility of the effect of the triazole on TA104 reversions was poor, TA→AT transversions were not eliminated as also contributing to the mutagenicity of these epoxides in this Salmonella strain. © 1993 Wiley‐Liss, Inc.
Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O‐acetyltransferase and nitroreductase activities
Authors: Oda Yoshimitsu , Yamazaki Hiroshi , Watanabe Mosahiko , Nohmi Takehiko , Shimada Tsutomu 
Published: February 2007

AbstractA highly sensitive umu test system for the detection of genotoxic activities of a variety of mutagenic nitroarenes has been developed using a new tester strain, Salmonella typhimurium NM3009 having high O‐acetyltransferase (O‐AT) and nitroreductase (NR) activities. The NM3009 was constructed by subcloning both the O‐AT and NR genes into plasmid vector pACYC184, and the resulting plasmid was introduced into the parent tester strain S. typhimurium TA1535/pSK1002 harboring an umuC‘‐’lacZ fusion gene. The induction of umuC gene expression could be monitored by measuring the cellular β‐galoctosidase activity produced by fusion gene. The purpose of the study was to evaluate whether the newly developed strain NM3009 is highly sensitive toward nitroarene compounds. The sensitivity of the strain NM3009 was compared with those of the parent TA1535/pSK1002 strain, the NR‐overexpressing strain NM1011, the NR‐deficient strain NM1000, the O‐AT‐over‐expressing strain NM2009, and the O‐AT‐defective strain NM2000. The newly developed NM3009 strain had about 13‐fold and 3‐fold higher activities for N‐AT and NR, respectively, than the original S. typhimurium TA1535/pS1002 strain. Among six strains tested, NM3009 showed the highest sensitivity toward such chemicals as 1‐nitronaphthalene, 2‐nitrofluorene, 3,7‐dinitro‐fluoranthene, 3‐nitrofluoranthene, 5‐nitroacenaphthene, 2‐nitronaphthalene, 1‐nitropyrene, 1,6‐dinitropyrene, 3,9‐dinitrofluoranthene, 4,4′‐dinitrobiphenyl, 1,8‐dinitropyrene, m‐dinitrobenzene, 2,4‐dinitrotoluene, and 1,3‐dinitropyrene. We have also found that the order of sensitivities to induce umuC gene expression toward a variety of nitroarenes was NM3009 > NM2009 > NM1011 > TA1535/pSK1002 > NM2000 > NM1000. These results suggest that the newly developed tester strain NM3009 is of great use for the detection of genotoxic activities of numerous carcinogenic and mutagenic chemicals including nitroarenes, which require NR and/or O‐AT for the activation. © 1993 Wiley‐Liss, Inc.
Modification of clastogenicity of three known clastogens by garlic extract in mice in vivo
Authors: Das Tandra , Roychoudhury Arati , Sharma Archana , Talukder Geeta 
Published: February 2007

AbstractThe anticlastogenic activity of crude extract of garlic (Allium sativum L.) was studied in bone marrow cells of mice. Male laboratory‐bred Swiss albino mice were given one of three concentrations of the freshly prepared extract (100 mg, 50 mg, and 25 mg/kg body weight) as a dietary supplement by gavage for 6 consecutive days. On the seventh day the mice were administered a single acute dose of two known clastogens, mitomycin C(1.5 mg/kg) and cyclophosphamide (25 mg/kg) or sodium arsenite (2.5 mg/kg), simultaneously with garlic extract. After 24 hr, chromosome preparations were made from the bone marrow cells. The endpoint studied were chromosomal aberrations and damaged cells. Garlic extract alone induced a low level of chromosomal damage. The clastogenicity of all three mutagens were reduced significantly in the animals which had been given garlic extract as dietary supplement. The extent of reduction was different for the three clastogens and may be attributed to the interaction with the different components of the extract. © 1993 Wiley‐Liss, Inc.
Correlation of frameshift mutagenicity with dna intercalation by CGS 20928A using an in vitro DNA unwinding assay
Authors: Mattes W. B. , Kapeghian J. C. , Lasinski E. R. , O'Lone S. D. , Puri E. C. , Matheson D. W. 
Published: February 2007

AbstractA compound's mutagenicity in different Salmonella tester strains can suggest its mechanism of reaction with DNA. Clear confirmation of such a mechanism, however, requires a direct test of the compound's reaction with DNA, often relying on specific in vitro studies. We report the use of a rapid in vitro test designed to measure DNA unwinding, a characteristic of DNA intercalators and many frameshift mutagens. CGS 20928A, an adenosine antagonist, produced a significant (<2‐fold) increase in revertants only for Salmonella tester strain TA1537, and only without metabolic activation. These data indicated that the compound was a direct acting frameshift mutagen and possibly intercalated into DNA. Our DNA unwinding assay indicated that at concentrations of <0.1 mM CGS 20928A behaved like known intercalating compounds in that it unwound DNA. These concentrations of compound are comparable to those found mutagenic to TA1537. By comparison, the frameshift mutagen and known intercalating compound 9‐aminoacridine unwound DNA in this assay in a concentration dependent fashion between 6–12 μM. ICR‐191, another acridine frameshift mutagen, also unwound DNA. A compound structurally related to CGS 20928A, which was not mutagenic in Salmonella tester strains, did not produce any DNA unwinding even at 10 mM. Because the assay uses microgram quantities of material, it should be ideal for screening small amounts of congeneric series suspected of frameshift mutagenicity. © 1993 Wiley‐Liss, Inc.
Chemico/biological investigation of contaminated sediment from the hamilton harbour area of Western Lake Ontario
Authors: Marvin C. H. , Allan L. , McCarry B. E. , Bryant D. W. 
Published: February 2007

AbstractHighly contaminated sediment from the Hamilton Harbour area of western Lake Ontario was examined using a bioassay‐directed fractionation methodology. A sediment sample was extracted using a Soxhlet apparatus and the resulting extract was fractionated into compound classes using an alumina clean‐up step and high performance liquid chromatographic techniques. The resulting fractions were subjected to bioassays using TA98‐ and TA100‐like strains modified by the inclusion of genes for the activating enzymes nitroreductase and O‐acetyl‐transferase. The majority of the mutagenic activity displayed by the sample extract was found to be present in the fraction containing the polycyclic aromatic hydrocarbons (PAH). Extracts of the PAH‐containing fraction displayed dramatically higher responses with the TA100 type strains with metabolic activation. Further separation of the PAH‐containing fraction showed the majority of the biological activity coeluted with PAH having molecular masses of 276, 278, and 302 amu. © 1993 Wiley‐Liss, Inc.
Genotoxic activity detected in soils from a hazardous waste site by the ames test and an SOS colorimetric test
Authors: McDaniels Audrey E. , Reyes Antolin L. , Wymer Larry J. , Rankin Clifford C. , Stelma Gerard N. 
Published: February 2007

AbstractTen soil samples from a hazardous waste site were compared for their genotoxic activity by the Ames test (Salmonella reverse mutation assay) and a modified SOS colorimetric test. Polynuclear aromatic hydrocarbons known to produce frameshift mutations were found in high levels in the soils. Salmonella typhimurium TA98, sensitive to frameshift mutations, was selected as the Ames tester strain. Escherichia coli K12 PQ37 (sulA::lacZ) was the SOS tester strain. Organic extracts were prepared from the soil samples by Soxhlet extraction. One set of the soil samples was extracted with methylene chloride and a second set with cyclohexane. Two criteria from reproducible dose‐related increases in response to the soil were used to compare the positive responses: 1) the concentrations required for doubling responses and 2) a minimum concentration required to produce statistically significant increases from background controls. Analysis of variance indicated that with S9 mix, Ames and SOS results were similar for the same soils and solvent extractions. However, without S9 mix, the SOS test was significantly more sensitive than the Ames test to the genotoxins extracted from the soils. Both the Ames and SOS tests detected lower concentrations of genotoxins in methylene chloride than in cyclohexane extracts. The simplicity of the method, reduction in expenses, and results within 1 working day all contribute to the advantages of the SOS test. © 1993 Wiley‐Liss, Inc.
Classification of mutations at the HLA‐A locus by use of the polymerase chain reaction
Authors: Joseph Grant , Grist Scott , Firgaira Frank , Turner David , Morley Alec 
Published: February 2007

AbstractWe investigated whether the polymerase chain reaction (PCR) could be used to determine the mechanism of mutation in lymphocyte clones mutated at the HLA‐A locus. Three polymorphisms, at Factor XIIIA, D6S109, and intron 3 of the HLA‐A gene, were used to study a series of clones previously characterised by Southern blotting (SB) at multiple loci on chromosome 6. For detection of loss of heterozygosity, the results of PCR and SB were concordant in 140 of 141 clones when polymorphism in the Factor XIIIA region was studied and in 144 of 145 clones when polymorphism in the HLA‐A gene was studied. For classification of the mechanism of mutation, PCR and SB gave the same result in 88 of 92 clones (96%) when a combination of the HLA‐A and Factor XIIIA polymorphisms was used and in 46 of 47 clones (98%) when a combination of the HLA‐A and D6S109 polymorphisms was used. The results indicate that PCR provides a simple and reliable method for categorising mutations at the HLA‐A locus as arising from mitotic recombination, deletion, or from presumptive minor changes within the gene. Rare events such as gene conversion, nondisjunction, or large deletions extending to the telomere will be misclassified. However, such events are rare for mutations at this locus. © 1993 Wiley‐Liss, Inc.
Time sequence of events leading to chromosomal aberration formation
Authors: Moore Ruth C. , Bender M. A 
Published: February 2007

AbstractInvestigations have been carried out which have measured the influence of the repair polymerases on the yield of different types of chromosomal aberrations. The studies were mainly concerned with the effect of inhibiting the polymerases on the yield of aberrations. The polymerases fill in single strand regions, and the fact that their inhibition affects the yield of aberrations suggests that single strand lesions are influential in aberration formation.The results indicate that—1. There are two actions of polymerases in clastogenesis. One is in their involvement in a G2 repair system, in which the pair of chromatids is concerned, and which does not yield aberrations unless the inhibition is still operating when the cells enter mitosis. The second also operates in G1 and S, and is such that when repair is inhibited, further damage accrues.2. The second action is affected by inhibiting polymerase but operates even when the repair enzymes are active.3. The production of chromosomal exchanges involves a series of reactions, some of which are reversible.4. The time span over which the reactions occur is much longer than has been envisaged previously (e.g., most of a cell cycle). © 1993 Wiley‐Liss, Inc.
Mechanism of chromosome exchange formation in human fibroblasts: Insights from “chromosome painting”
Authors: Brown J. M. , Evans J. W. , Kovacs M. S. 
Published: February 2007

AbstractWe have used the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with a library for human chromosome 4 to analyze the rate of rejoining of chromosome breaks and development of exchange aberrations in AG1522 human fibroblasts. AG1522 cells were irradiated in plateau phase with 10 Gy and fused with mitotic HeLa cells either immediately after irradiation or at intervals up to eight days later. The slides were then hybridized with the chromosome 4 library and unrejoined breaks and exchange events (visualized as bicolor chromosomes) scored in these cells. At the earliest time point after irradiation, the number of exchange events in the irradiated cells was low, but increased with kinetics similar to that of the joining of the breaks. Furthermore, when we analyzed those cells which had exchange events for their distribution, almost all of the cells initially contained one exchange event (1 bicolor chromosome). As time progressed, the number of cells containing exchanges with two exchange events per cell increased as the number with one exchange event per cell decreased. Extrapolation of the number of exchange events to zero time (with an estimate of 20 min for the fusion and condensation times) gave a value consistent with zero exchanges at zero time after irradiation. In a separate experiment, we also scored AG 1522 cells at the first metaphase after a dose of 6 Gy and were able to show that as many as 50% of the complete exchanges were non‐reciprocal in nature, that is, the two broken ends of a single break in chromosome 4 joined to two different chromosomes. These data support the classical breakage‐and‐reunion model rather than the Revell Exchange Theory of exchange formation. © 1993 Wiley‐Liss, Inc.
Histone shuttle driven by the automodification cycle of poly(ADP‐ribose) polymerase
Authors: Althaus Felix R. , Höfferer Liane , Kleczkowska Hanna E. , Malanga Maria , Naegeli Hanspeter , Panzeter Phyllis , Realini Claudio 
Published: February 2007

AbstractIn mammalian cells, the incision step of DNA excision repair triggers a dramatic metabolic response in chromatin. The reaction starts with the binding of a zinc‐finger protein, i.e. poly‐(ADP‐ribose)polymerase to DNA nicks, activation of four resident catalytic activities leading to poly(ADP‐ribose) synthesis, conversion of the polymerase into a protein modified with up to 28 variably sized ADP‐ribose polymers, and rapid degradation of polymerase‐bound polymers by poly(ADP‐ribose)glycohydrolase. This automodification cycle catalyzes a transient and reversible dissociation of histones from DNA. Shuttling of histones on the DNA allows selected other proteins, such as DNA helicase A and topoisomerase I, to gain access to DNA. Histone shuttling in vitro mimics nucleosomal unfolding/refolding in vivo that accompanies the postincisional steps of DNA excision repair. Suppression of the automodification cycle in mammalian cells prevents nucleosomal unfolding and nucleotide excision repair. © 1993 Wiley‐Liss, Inc.
Assessing the risk of heritable gene mutation in mammals: Drosophila sex‐linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cells
Authors: Bentley Karin S. , Sarrify Awni M. , Cimino Michael C. , Auletta Angela E. 
Published: February 2007

AbstractThe former U.S. EPA OPPT tiered test scheme for heritable gene mutations included the Drosophila sex‐linked recessive lethal (SLRL) test in which positive results triggered the mouse specific locus (MSL) test. However, review of available literature indicated that the evaluation of mutations in the germ cells of this insect is not a good predictor of the risk of heritable gene mutations in mammals. The database contained 29 compounds for which there were conclusive MSL test results in either spermatogonial and/or postspermatogonial cells. Results in the SLRL test were available for 27 of those compounds. Of the 24 SLRL‐positive chemicals, only 13 (54%) induced heritable mutations in mice; the three SLRL‐negative compounds were nonmutagenic in mouse germ cells. The overall concordance between the two tests was 59%. In contrast, results of unscheduled DNA synthesis (UDS: 18 chemicals) and alkaline elution (AE: 14 chemicals) assays in rodent testicular cells following in vivo exposure correlated well with results in the MSL test (83% and 86%, respectively). MSL test results in spermatogonia and postspermatogonia were also compared separately to the SLRL, UDS, and AE assays. The concordances for the two cell types in the SLRL relative to the MSL test were 36% and 79%, respectively, indicating that the SLRL test is extremely poor in predicting heritable gene mutations in mammalian spermatogonia. Concordances for UDS and AE assays relative to MSL test results in spermatogonia (53% and 54%, respectively) and postspermatogonia (91% and 100%, respectively) were greater. Based on these analyses, the U.S. EPA OPPT has revised its tiered test scheme using assays for interaction with gonadal DNA (e.g., UDS and AE) in place of the SLRL test. © 1994 Wiley‐Liss, Inc.