bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS Chromotest
Authors: De Méo M. , Vanelle P. , Bernadini E. , Laget M. , Maldonado J. , Jentzer O. , Crozet M. P. , Duménil G. 
Published: February 2007

AbstractThe mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives have been evaluated by using modified versions of the Ames test and the SOS Chromotest. Salmonella typhimurium tester strain TA 100 was used with and without metabolic activation in the Ames test and Escherichia coli tester Strain PQ 37 was used with and without metabolic activation in the SOS Chromotest. Including metronidazole and dimetridazole, 45 derivatives were mutagenic and genotoxic. The mutagenic potencies (MP) ranged from 0.127 to 53,717 revertants/nmol while the SOS induction powers (SOSIP) ranged from 0.00131 to 107 IF/nmol. The overall correlation between MP and SOSIP was r = 0.845 (n = 84) as calculated by linear regression analysis. A higher correlation was observed between MP and SOSIP without the S9 mix than with it. Among the imidazole derivatives, the 5‐nitroimidazoles with a lactam ring at the 2‐position showed the highest MP and SOSIP. The presence of a nitro group at the 5‐position was critical for the mutagenicity and the genotoxicity of the derivatives. Substituents at the 1‐ and 2‐positions were also found to modulate these activities.
Chemical mutagenesis testing in Drosophila: VIII. Reexamination of equivocai results
Authors: Mason J. M. , Valencia R. , Zimmering S. 
Published: February 2007

AbstractTwelve percent of the chemicals tested for mutagenicity by the National Toxicology Program (NTP) using the Drosophila sex‐linked recessive lethal assay have been classified as producing equivocal results. We have reexamined the published data and the criteria used to determine mutagenicity in light of the historical distribution of the concurrent negative controls for this project. Many of the chemicals that originally produced equivocal results have been retested under code. As a result of changes to incorporate a comparison with the historical control in the algorithm used to determine mutagenicity and as a result of new data accumulated, 4 of the 25 chemicals that gave equivocal results are judged to be mutagenic, and 11 others are judged to be nonmutagenic under our test conditions.
Effects of plate preparation on results in microbial mutation assays
Authors: Majeska Jenness B. , McGregor Douglas B. 
Published: February 2007

AbstractGlucose autoclaved in an alkaline phosphate solution (heated glucose + salts, HGS) results in the production of a moiety that is nonmutagenic but can interact with a series of 4‐[2‐(aryl)ethenyl]‐2,6‐dimethylphenols to result in an increase in bacterial revertants that is dependent on the amount of HGS in the minimal agar plates. The reaction between the HGS and the chemical to form a mutagen is independent of the presence of bacteria, does not result in a nutritive analog to enhance growth of the auxotrophic bacteria, and is effective only in Salmonella typhimurium and Escherichia coll strains that contain the plasmid pKM101. A sufficient amount of this glucose product may be formed in normal plate preparation to produce apparent mutagenic activity of these chemicals.
Genetic and environmental influences on baseline SCE
Authors: Hirsch Betsy A. , Sentz Karen K. , McGue Matt 
Published: February 2007

AbstractPrevious population‐based studies have identified subject characteristics that, when combined, can account for ∼20% of the observed interindividual variation in baseline SCE rates. In the present investigation, a classic twin study design was used to address the issue of the relevance of genetic factors to baseline SCE rates and to identify other demographic, hematologic, and exposure variables predictive of SCE rate. Questionnaire data and peripheral blood samples from 136 monozygotic and 88 dizygotic twins (age range: 25–81 years) were obtained. Among the large number of variables examined, univariate analyses (including ANOVA tests for the categorical variables and Pearson‐product moment correlations for the quantitative variables) revealed smoking status, coffee drinking status, sex, white blood cell count, and absolute numbers of lymphocytes and neutrophils to have significant effects on SCE rates. A stepwise multiple regression analysis showed that together, smoking and coffee drinking status entered at the first step accounted for 21% of the observed variance in SCE, with a further 6% being contributed by the demographic and hematologic variables added in subsequent steps. Finally, the twin analyses showed that after adjustment of the data set for smoking and other significant predictors, genetic factors accounted for ∼30% of the variation in SCE rates. Thus these data support the hypothesis of a significant genetic influence on baseline SCE. © 1992 Wiley‐Liss, Inc.
Molecular analysis of mutations induced by the intercalating agent ellipticine at the hisd3052 allele of salmonella typhimurium TA98
Authors: Demarini David M. , Abu‐Shakra Amal , Gupta Ranjan , Hendee Linda J. , Levine Jessie G. 
Published: February 2007

AbstractWe have used DNA colony hybridization, the polymerase chain reaction (PCR), and direct DNA sequencing to determine the mutations induced by the intercalating agent ellipticine in Salmonella typhimurium TA98 in the presence of S9. Of 400 ellipticine‐induced revertants that were selected at a mutant yield that was ninefold over the background, 85.5% contained a GC or CG deletion within a common CGCGCGCG hotspot; this deletion occurred among 47% of the spontaneous revertants. In addition to this hotspot, the ellipticine spectrum contained two deletion warmspots that reside opposite each other in looped‐out regions of a possible DNA secondary structure. Ellipticine and its metabolites likely revert Salmonella strain TA98 by forming DNA adducts that promote slippage‐mismatches and by stabilizing these slipped mismatched sequences via intercalation. The involvement of these mechanisms, along with a likely role for DNA secondary structures and a possible role for DNA gyrase, may account for the site specificity exhibited by ellipticine in strain TA98. © 1992 Wiley‐Liss, Inc.
Mitogenic activity of quinoline to the rat, mouse, and guinea pig liver: Empirical correlations with hepatic carcinogenicity
Authors: Lefevre P. , Ashby J. 
Published: February 2007

AbstractPrevious studies have shown that the rat liver carcinogen quinoline is essentially nongenotoxic to the rat liver in vivo. Those studies also established it as a potent mitogen to rat liver. The present experiments have established quinoline as a mitogen to the mouse liver, a tissue in which it is also reported to be carcinogenic. In contrast, quinoline is reported to be noncarcinogenic to the guinea pig liver, and the present data establish it to be essentially nonmitogenic to the guinea pig liver. It is concluded that the mitogenicity of quinoline correlates better with its hepatocarcinogenic properties than does its genotoxicity in vivo. © 1992 Wiley‐Liss, Inc.
Mutations causing defective splicing in the human hprt gene
Authors: Andersson Björn , Hou Sai‐Mei , Lambert Bo 
Published: February 2007

AbstractTen intron mutations and one exon mutation giving rise to defective splicing in the human gene for hypoxanthine phosporibosyl transferase (hprt) in T‐lymphocytes have been characterized. the splicing mutants were detected by PCR amplification of hprt cDNA and direct sequencing. Nine of the mutants showed skipping of whole exons or parts of exons in the cDNA, one mutant had an inclusion of an intron sequence into the cDNA, and one mutant showed both inclusion of an intron sequence and skipping of exons as well as a normal cDNA. Genomic PCR and direct sequencing of the splice sites involved showed one deletion of three base pairs and 10 different single base alterations to be responsible for these splice alterations. One mutation in the last base pair of exon 6 causing skipping of the entire exon 6 was found, whereas an identical mutation in the last base pair of exon 2 caused no aberrant splicing. It was also found that a deletion mutation in the pyrimidine rich stretch of the acceptor site of intron 7 caused skipping of the entire exon 8, whereas a base substitution in the last base of intron 7 caused exclusion of only the first 21 base pairs of exon 8 as a result of the activation of a cryptic acceptor site in exon 8. The results show that many different types of mutations at several different sites can cause splicing errors in the hprt gene and that the sequence differences between the splice sites influence the possible spectrum of mutations in each site. © 1992 Wiley‐Liss, Inc.
Effects of captan on dna and dna metabolic processes in human diploid fibroblasts
Authors: Snyder Ronald D. 
Published: February 2007

AbstractThe fungicide Captan has been examined for its effects on DNA and DNA processing in order to better understand the genotoxicity associated with this agent. Captan treatment resulted in production of DNA single strand breaks and DNA‐protein cross‐links and elicited an excision repair response in human diploid fibroblasts. Captan was also shown to inhibit cellular DNA synthesis and to form stable adducts in herring sperm and human cellular DNA. Misincorporation of nucleotides into Captan‐treated synthetic DNA templates was significantly elevated in an in vitro assay using E. coli DNA polymerase I, suggesting that DNA adduct formation by Captan could have mutagenic consequences. In sum, these studies demonstrate that Captan is capable of interacting with DNA at a number of levels and that these interactions could provide the basis for Captan's genotoxicity. The extreme cytotoxicity of this fungicide, however, could be due to other cellular effects since at the IC50 for cell killing, approximately 0.8 μM, none of the above genotoxic events could be detected by the methods employed. © 1992 Wiley‐Liss, Inc.
Posttreatment with sodium arsenite alters the mutational spectrum induced by ultraviolet light irradiation in chinese hamster ovary cells
Authors: Yang Jia‐Ling , Chen Mei‐Fang , Wu Cheng‐Wen , Lee Te‐Chang 
Published: February 2007

AbstractArsenic, a potent carcinogen, fails to induce gene mutations in mammalian cells. However, posttreatment of ultraviolet light (UV) irradiated cells with sodium arsenite synergistically enhances the mutation frequency on the hypoxanthine (guanine) phosphoribosyltransferase locus. To investigate the molecular mechanism of the comutagenic effects of sodium arsenite, we characterized the alterations of nucleotide sequences in 30 UV‐induced and 39 sodium arsenite enhanced hprt mutants from Chinese hamster ovary K1 cells by direct sequencing of mRNA‐PCR amplified cDNA. The majority of sequence alterations derived from UV irradiation (80%) and from sodium arsenite posttreatment (70%) were single base substitutions. UV irradiation induced all types of base substitutions. Among them, 57% were transversions. The frequency of transversions increased to 70% in sodium arsenite enhanced mutants. While base substitutions observed in UV‐induced mutants were evenly distributed along with the whole coding region, exons 3 and 8 were most frequently mutated in sodium arsenite enhanced mutants. Sodium arsenite posttreatment did not alter the strand bias for mutation induction, i.e., 73% and 78%, of the mutations were located on the non‐transcribed strand in UV‐induced and sodium arsenite enhanced mutants, respectively. In contrast to UV‐induced mutations, bases at the 5' position of TT and the 3' position of CT sequences were the most frequent mutation sites observed in sodium arsenite enhanced mutants. We hypothesize that sodium arsenite may interfere with the process of mutation fixation of TT and CT dimers during DNA replication. © 1992 Wiley‐Liss, Inc.
Optimization of the concurrent assay for gene mutations and chromosomal aberrations in vivo: Expression time in rats
Authors: Khan Mohammed A. , Heddle John A. 
Published: February 2007

AbstractEthylnitrosourea was used as a model mutagen to determine the time at which the most mutants and chromosomal aberrations could be detected. Primary fibroblasts derived from Fischer (F344) rats that had been mutagenized by ethylnitrosourea in vivo, were grown in culture and sampled at increasing intervals to analyze, quantitatively, gene mutations and chromosomal aberrations. Since ethylnitrosourea reacts very quickly and the cells were isolated five hours after treatment, expression time represents the intracellular processes involved, not the pharmacokinetics of the mutagen. A thioguanine selection procedure was used to quantify gene mutations. A cytochalasin B technique for micronuclei was used to quantify chromosomal aberrations. A significant increase in the number of mutations was observed on the ninth day in an experiment wherein sampling was done at increasing intervals of three days. One of two experiments wherein sampling was done at increasing intervals of five days showed maximum number of mutations in dishes plated with cells, exposed to maximum dose (200 mg/ kg), on the tenth day for selection. Cells that received dose 100 mg/kg on the contrary produced maximum number of mutant colonies in dishes that were plated on the 20th day for selection. A repeat of the 5‐day interval experiment showed maximum number of mutant colonies in dishes selected on the tenth day, irrespective of the dose used. The number of micronuclei reached a maximum on the third day. © 1992 Wiley‐Liss, Inc.
Chlorophyllin‐enhanced excretion of urinary and fecal mutagens in rats given 2‐amino‐3‐methylimidazo[4, 5‐f]quinoline
Authors: Dashwood Roderick , Liew Christina 
Published: February 2007

AbstractSodium/copper chlorophyllin (CHL) is a water‐soluble derivative of chlorophyll that exhibits antimutagenic activity in several short‐term genotoxicity assays and inhibits carcinogen‐DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague‐Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2‐amino‐3‐methylimidazo‐[4, 5‐f]quinoline (IQ) by oral gavage. Rats pre‐treated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was <4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with β‐glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a “desmutagen” or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability. © 1992 Wiley‐Liss, Inc.
Characteristics of spontaneous and induced specific‐locus mutation in the ad‐3 region of neurospora crassa: Utilization in genetic risk assessment
Authors: De Serres Frederick J. 
Published: February 2007

AbstractData from experiments on the induction of specific‐locus mutations in model systems are utilized in genetic risk assessment to estimate potential adverse effects in the human population. In such assessments with radiation or chemical mutagens, the following information is required: (1) spontaneous and induced forward‐mutation frequencies, (2) dose‐response curves for the overall induction of specific‐locus mutations, (3) genetic characterization of spontaneous and induced mutations, and (4) dose‐response curves for the different genotypic classes. Specific‐locus assays in most eukaryote assay systems provide only portions of the information required for genetic risk assessment. In recognition of the need for a more comprehensive data base, a model system was developed for specific‐locus studies in Neurospora crassa. The adenine‐3 (ad‐3) specific‐locus assay was modeled after the 2 gene, morphological specific‐locus assay in the dilute‐short‐ear region of the mouse, and it detects forward‐mutations at two closely linked loci: ad‐3A and ad‐3B. The ad‐3 assay system has provided precise dose‐response curves not only for inactivation, but also the overall induction of ad‐3 mutations. The utilization of this assay in experiments with radiation or chemical mutagens has provided a data base on the induction and genetic characterization of specific‐locus mutations that is unique among eukaryotic organisms. In this assay, gene/point mutations, multilocus deletion mutations, and 3 different classes of multiple‐locus mutations can be identified. The latter consist of specific‐locus mutations associated with recessive lethal mutations located either closely linked to the ad‐3 region or elsewhere in the genome. The overall data base on the heterozygous effects of X‐ray‐induced ad‐3 mutations demonstrates that such effects are allele specific, genotype specific, and locus specific. There are probably a variety of mechanisms by which the heterozygous effects of individual allelic mutations at different genetic loci can be affected. In conclusion, unless the frequencies of all of the different classes of induced specific‐locus mutations are determined, and utilized in genetic risk assessment exercises, the risk of human exposure to environmental mutagens may be grossly underestimated. © 1992 Wiley‐Liss, Inc.
Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes
Authors: Chang Lina W. , Daniel F. B. , Deangelo Anthony B. 
Published: February 2007

AbstractAn alkaline unwinding assay was used to quantitate the induction of DNA strand breaks (DNA SB) in the livers of rats and mice treated in vivo, in rodent hepatocytes in primary culture, and in CCRF‐CEM cells, a human lymphoblastic leukemia cell line, following treatment with tri‐ (TCA), di‐ (DCA), and mono‐ (MCA) chloroacetic acid and their corresponding aldehydes, tri‐ (chloral hydrate, CH), di‐ (DCAA) and mono‐ (CAA) chloroacetaldehyde. None of the chloroacetic acids induced DNA SB in the livers of rats at 4 hr following a single administration of 1–10 mmole/kg. TCA (10 mmole/kg) and DCA (5 and 10 mmole/kg) did produce a small amount of strand breakage in mice (7% at 4 hr) but not at 1 hr. N‐nitrosodiethylamine (DENA), an established alkylating agent and a rodent hepatocarcinogen, produced DNA SB in the livers of both species. TCA, DCA, and MCA also failed to induce DNA strand breaks in splenocytes and epithelial cells derived from the stomach and duodenum of mice treated in vivo. None of the three chloroacetaldehydes induced DNA SB in either mouse or rat liver. The continuous exposure of mice to 5 g/L DCA in the drinking water for 7 and 14 days did not induce appreciable hepatic DNA SB (< 10% at 14 days), although peroxisome proliferation, as evidenced by an increased cyanide‐insensitive palmitoyl CoA oxi‐dase (PCO) activity, was stimulated to 490% (7 days) and 652% (14 days) of control. Under this protocol, DENA (0.1 g/L) produced DNA damage after both 7 days (73% of control) and 14 days (57% of control). Similarly, long‐term exposure of rats (30 weeks) to 2 g/L DCA in the drinking water, a level that increased PCO activity to 364% of the control value, exhibited no DNA damage. Both the chloroacetic acids and the chloroacetaldehydes were ineffective in inducing DNA SB in cultured rat and mouse hepatocytes at concentrations below those that yielded cytotoxicity. The chloroacetic acids were also ineffective in the CCRF‐CEM cells. However, two of the chloroaldehydes, DCAA and CAA, did induce DNA SB in the CCRF‐CEM cells at concentrations that did not decrease the cell viability after 2 hr of treatment. Prior incubation of DCAA and CAA with a rat S9 liver homogenate eliminated much of the DNA damaging activity. These studies provide further evidence that the chloroacetic acids lack genotoxic activity not only in rodent liver, a tissue in that they induce tumors, but in a variety of other roden tissues and cultured cell types. Two of the chloroacetaldehydes, DCAA and CAA, are direct acting DNA damaging agents in CCRF‐CEM cells, but not in liver or splenocytes in vivo or in cultured hepatocytes. CH showed no activity in any system investigated. © 1992 Wiley‐Liss, Inc.
Induction of micronuclei by bleomycin in G0 human lymphocytes: II. Potentiation by radioprotectors
Authors: Hoffmann George R. , Colyer Shirley P. , Littlefield L. Gayle 
Published: February 2007

AbstractDimethylsulfoxide (DMSO) and WR‐1065 are radioprotectors, in that they reduce the effectiveness with which ionizing radiation causes genetic damage. Unlike their protective effects with radiation, these agents potentiate the induction of micronuclei by bleomycin in the cytokinesis‐block assay in G0 human lymphocytes. High concentrations of DMSO (1 M) are required to cause potentiation. In contrast, WR‐1065 causes dose‐dependent potentiation at relatively low concentrations (1.25 to 10 mM). Cytogenetic analysis supports the results from the micronucleus assay, showing higher levels of genetic damage induced by the combination of bleomycin with DMSO or WR‐1065 than by bleomycin alone. Possible mechanisms of potentiation are proposed. © 1993 Wiley‐Liss, Inc.
Effects of methyl methanesulfonate on mouse sperm chromatin structure and testicular cell kinetics
Authors: Evenson Donald P. , Jost Lorna K. , Baer Rebecca K. 
Published: February 2007

AbstractEffects of methyl methanesulfonate (MMS) on mouse testicular cell kinetics and sperm chromatin structure were determined flow cytometrically. Mice were exposed to a single ip injection of saline containing 0 or 150 mg/kg MMS, Relative ratios of 1N, 2N and 4N testicular cells were not affected until 22 days postexposure. Ratios of 1N cell types were altered from 13 to 22 days and were near normal by 25 days. This study revealed an MMS induced alteration of chromatin structure in testicular, elongated spermatids by the sperm chromatin structure assay (SCSA), a flow cytometric measure of the susceptibility of acridine orange stained sperm DNA to denaturation in situ. The SCSA also detected alterations in cauda sperm chromatin structure at 3 days, which was 8 days prior to alterations in sperm head morphology, indicating the increased sensitivity of the SCSA. SCSA data were practically similar whether measuring either fresh or frozen/thawed sperm, or whether measured by two different types of flow cytometers: a) laser driven, orthogonal optical axis; or b) low cost mercury arc lamp system with epiillumination. The data support the model of Sega and Owens [Mutat Res 111:227–244:1983] that MMS alkylates cysteine ‐SH groups in sperm protamines, thereby destabilizing sperm chromatin structure and leading to broken chromosomes and mutations. © 1993 Wiley‐Liss, Inc.