摘要:

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

ISSN:0893-6692    

DOI:10.1002/em.2850220203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTreatment of C57BL/6J mice with an epoxide, glycidyl 1‐naphthyl ether (GNE), resulted in an average of a 3.4‐fold increase in frequency of 6‐thioguanine‐resistant mutants of mouse spleen T‐lymphocytes. In similar experiments with the epoxide trichloropropylene oxide, no increase in mutant frequency was found. To determine the kind and location of mutations in the coding region of the hypoxanthine phosphoribosyl transferase (HPRT) gene, 26 GNE‐induced mutants and 17 spontaneous mutants were analyzed by direct sequencing of polymerase chain reaction amplified cDNA. Among the GNE‐induced mutants, HPRT cDNA was present in 22, while that from 4 could not be detected. Among the spontaneous mutants, HPRT cDNA was present in 15 and absent in 2. Among GNE‐induced mutants, base substitution in HPRT occurred in 15 of 22 mutants analyzed. Nine of 15 base substitutions involved TA base pairs, primarily TA→CG transitions. Base substitutions were found throughout exons 3–7 but 46% of substitutions were located in exon 3 and one frameshift mutation involving a GC base pair in exon 3 was also observed. Among the spontaneous mutants, base substitutions of HPRT occurred in 7 of 15 mutants analyzed with 6 of 7 base substitutions involving a TA base pair and another 2 of the 15 mutants showed a 4 base pair deletion. The base substitution spectrum in GNE‐induced mutants was different from that of the spontaneous mutants.

ISSN:0893-6692    

DOI:10.1002/em.2850220204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe Ames Salmonella/microsome assay remains the most widely used microbial test for genotoxicity. In this article, we describe a microcomputer program developed to fit a linear‐exponential dose‐response model to Ames assay data for established mutagens. The model includes a linear term to describe the mutagenic effects of the test agent at low to moderate doses and an exponential attenuation factor to accommodate downturns at high doses due to cytotoxicity. Quasi‐likelihood methods are used to obtain estimates of the unknown model parameters, thereby avoiding the need to fully specify the distribution of the experimental data. This method of estimation also allows for extra‐Poisson variation that is characteristic of counts of mutant colonies of bacteria observed in the Ames assay. The particular linear‐exponential model used here was developed for use in the analysis of a recent large‐scale collaborative trial using the Ames assay sponsored by the International Programme on Chemical Safety. The use of our program is illustrated using sample data sets taken from that collaborative study. © 1993 Wil

ISSN:0893-6692    

DOI:10.1002/em.2850220205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAlthough the genotoxic potential of styrene is known, very limited information is available regarding its dose‐dependent genotoxic response to human blood lymphocytes and how such response correlates with different metabolic events in whole blood lymphocytes. The present study was therefore carried out to study such a relationship using in vitro human blood lymphocytes from healthy volunteers. To study genotoxic response to styrene, sister chromatid exchanges (SCEs), cell cycle, and cell survival were analyzed. Lymphocytes were cultured for 72 hr in the presence of different concentrations of styrene (0–1,000 μM). Twenty‐four hr before harvest, BrdU (5 μg/ml) was added to assess the increase in SCEs and cell cycle delay. Both the SCE frequency and the cell cycle length were increased linearly with increasing concentrations of styrene up to 200 μM, without addition of any exogenous metabolizing system. Above 200 μM, no further increase in genotoxic response occured. The range of concentrations (10–200 μM) at which increase of cell cycle length due to styrene was observed did not impair the viability of the cells, suggesting that such cell cycle delay is a genotoxic‐related event and not caused by cytotoxicity. In vitro metabolic transformation of styrene in whole‐blood lymphocyte cultures without the presence of any exogenous metabolic activation system showed the formation of a reactive intermediate, styrene 7,8‐oxide, to be capacity‐limited, as verified from a nonlinear increase in the formation of styrene glycol. The value of such metabolic parameter reached a plateau above 200 μM styrene. The same phenomenon of saturation has also been observed with regard to other metabolic effects due to styrene in whole blood lymphocytes in culture, such as dose‐dependent increase in lipid peroxidation and depletion of blood lymphocyte glutathione. Based on the relationship between the formation of different metabolic events and the genotoxicity of styrene, it may be possible that the genotoxic properties of styrene in human blood lymphocytes may be mediated initially not only by the formation of the presumably reactive styrene 7,8‐oxide, but also by that of a reactive oxygen species as well. However, the present data are not sufficient enough to definitely identify the role of reactive oxygen species in such toxicity and therefore it warrants further stud

ISSN:0893-6692    

DOI:10.1002/em.2850220206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTo assess the mutagenic potential of isopropanol, an in vitro Chinese hamster ovary (CHO) cell/HGPRT gene mutation assay and a bone marrow micronucleus study in mice were conducted. In the CHO/HGPRT assay, concentration levels ranged from 0.5 to 5.0 mg/ml. No elevated mutant frequencies attributable to treatment were observed in the test under either activated or non‐activated conditions. In the micronucleus assay, mice were injected intraperitoneally (IP) with either 350, 1,173, or 2,500 mg/kg of isopropanol at constant volumes of 10 ml/kg. No increased incidence of micronuclei was observed in bone marrow polychromatic erythrocytes (PCEs) harvested at 24, 48, or 72 hr post‐dosing. In both assays, negative and positive control mutant frequencies were within historical control ranges. These results, in conjunction with previously published data, clearly demonstrate that isopropanol is not a mutagen. © 1993 Wiley‐Lis

ISSN:0893-6692    

DOI:10.1002/em.2850220207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe micronucleus test is used widely as an in vivo short‐term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen‐induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1‐dimethylhydrazine (DMH) 12–24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals—benzo(a)pyrene, 2‐naphthylamine—was also observed following pretreatment with cobalt dichloride. © 1993 W

ISSN:0893-6692    

DOI:10.1002/em.2850220208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe various causative and mechanistic phenomena associated with aneuploidy induction require considerable investigation to better understand the etiology of chromosome missegregation. We investigated the potential of vinblastine sulfate, pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate to induce numerical and structural chromosome changes in female mouse germ cells. Superovulated ICR mice were administered the compounds either by intraperitoneal injection or oral gavage, and oocytes were collected and processed for cytogenetic analysis 17 hr later. Vinblastine sulfate, administered i.p., induced a significant increase in the frequency of ovulated Ml oocytes and of hyperploid Mll oocytes compared to controls, but did not increase the frequency of structural aberrations. Pyrimethamine, diethylstilbestrol diphosphate, and chloral hydrate did not increase the frequency of numerical or structural chromosome changes in female mouse germ cells. © 1993 Wiley‐Liss, I

ISSN:0893-6692    

DOI:10.1002/em.2850220209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTen soil samples from a hazardous waste site were compared for their genotoxic activity by the Ames test (Salmonellareverse 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 typhimuriumTA98, sensitive to frameshift mutations, was selected as the Ames tester strain.Escherichia coliK12 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,

ISSN:0893-6692    

DOI:10.1002/em.2850220210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850220211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850220212

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY