bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of theSalmonella(Ames) test,Umutests, and the sos chromotests for detecting genotoxins
Authors: McDaniels A. E. , Reyes A. L. , Wymer L. J. , Rankin C. C. , Stelma G. N. 
Published: February 2007

AbstractThe limits of detection of 10 genotoxins representing 7 chemical classes with varying structures and modes of action were compared using the Ames test (Salmonellaplate‐incorporation test) with 2 tester strains, 2 standard colorimetric methods (theumutest and SOS Chromotest), and modifications of theumuand SOS Chromotests developed during the course of this study. The purpose of the study was to determine the sensitivity and reproducibility of each of the six methods. The sensitivities of the methods were compared using two criteria: the concentrations required for doubling responses, and the minimum concentrations required to produce statistically significant increases from background controls. The Ames test with strains TA98 and TA100 was ranked as the most sensitive method more often than the others, but the results indicated that theumutests were statistically equivalent to the Ames test. The original SOS Chromotest kit method was highly sensitive in detecting the direct acting genotoxins, but neither SOS test was as sensitive as the other methods in detecting indirect acting genotoxins. Theumumicrotiter plate test is the least expensive of the assays and would be the most suitable for screening large numbers of environmental samples.
On the use of excision repair defective cells in the wing somatic mutation and recombination test in Drosophila melanogaster
Authors: Graf Ulrich , Hall Colin B. , Schaik Nancy Van , Aaron C. S. 
Published: February 2007

AbstractTen chemical mutagens were tested in the wing somatic mutation and recombination test in Drosophila melanogaster. This assay makes use of genetic markers expressed on the wing of adult flies. Larvae which are trans‐heterozygous for mwh (multiple wing hairs) and flr (flare) were fed with the compounds either acutely (2, 4, or 6 hr) or chronically (48 or 72 hr), or were treated by inhalation (1 hr). Genetic changes induced in the somatic cells of the wing imaginal discs lead to the formation of mutant clones on the wing (mwh and/or flr). Single spots are produced by point mutation, chromosome breakage, and mitotic recombination; twin spots are produced exclusively by mitotic recombination. All 10 mutagens belonging to different chemical classes were clearly positive in this assay. However, the choice of the optimal treatment conditions (concentration of compound, duration of treatment, age of larvae at treatment) is essential. Eight of the compounds were also tested in excision repair defective cells by introducing the mei‐9L1 mutation into the test system. This seems not to improve the detection capacity of the assay, mainly because only small spots are found in excision repair defective wings. In addition, the frequencies of spots in these wings are enhanced four to five times, which makes the scoring more tedious. For these and other practical reasons the use of this specific cross is not recommended in the wing spot test for routine screening purposes.
An evaluation of the cho/hgprt mutation assay involving suspension cultures and soft agar cloning: Results for 33 chemicals
Authors: Oberly T. J. , Rexroat M. A. , Bewsey B. J. , Richardson K. K. , Michaelis K. C. , Casciano D. A. 
Published: February 2007

AbstractThe Chinese hamster ovary cell assay (CHO), which measures forward mutation at the HGPRT locus, is used in several laboratories for the detection of mutagens. A procedure involving treatment of CHO cells in suspension culture and mutant selection in soft agar cloning has been developed (Oberly TJ, Bewsey BJ, Probst GS (1987): Mutat Res 182:99—111). In order to evaluate the effectiveness of these modifications, 33 chemicals representing six chemical classes were tested, and the results were compared to findings obtained in other tests for genotoxicity at Lilly Research Laboratories (LRL). A positive response was obtained with 21 chemicals, all of which are recognized mutagens. Of the 12 compounds that produced negative results, 4 were considered to be mutagens and/or carcinogens. Twelve of the compounds mentioned in this report have been previously tested in the CHO/HGPRT assay by other laboratories, and the results showed strong agreement between laboratories. These findings support the conclusion that the use of suspension cultures and soft agar cloning in the CHO assay provides a sensitive test for the identification of mutagens and is a viable alternative to the traditional monolayer procedure of O'Neill et al. (O'Neill JP, Couch DB, Machanoff R, San Sebastian JR, Brimer PA, Hsie AW (1977): Mutat Res 45:103—109).
Chromosome aberration and sister chromatid exchange tests in chinese hamster ovary cells in vitro. V: Results With 46 Chemicals
Authors: Loveday K. S. , Anderson B. E. , Resnick M. A. , Zeiger E. , Holden H. E. 
Published: February 2007

AbstractForty‐six coded chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary (CHO) cells using a standard protocol with and without exogenous metabolic activation. Sixteen chemicals were negative and 15 were positive in both assays; 15 were positive for SCEs only (one chemical that was positive for SCEs was equivocal for ABs), and no chemicals induced ABs only. The effect of cell harvest time on the ability to detect the induction of ABs was examined for 18 chemicals. Seven chemicals produced a positive response using both standard and extended harvest times, five were positive only using an extended harvest time, and six were negative using both harvest times. The relationship between cell cycle delay and SCE induction was also examined, and the two appear to be unrelated.
Genotoxicity of the fungicide dichlofluanid in seven assays
Authors: Heil J. , Reifferscheid G. , Hellmich D. , Hergenröder M. , Zahn R. K. , Setlow R. B. 
Published: February 2007

AbstractSeven different endpoints for detection of genotoxicity have been used to demonstrate the DNA‐altering properties of Dichlofluanid, a fungicide commonly used in viticulture pest control. Each endpoint (DNA synthesis inhibition test, alkaline viscosimetry, umu‐test, alkaline filter elution, FADU‐test, 32P‐postlabeling, and electron microscopy) shows clear evidence of genotoxicity. These data indicate that application of the fungicide dichlofluanid may be mutagenic and/or carcinogenic for exposed humans.
Single‐strand breaks, chromosome aberrations, sister‐chromatid exchanges, and micronuclei in blood lymphocytes of workers exposed to styrene during the production of reinforced plastics
Authors: Mäki‐Paakkanen J. , Norppa Hannu , Walles S. , Osterman‐Golkar S. , Oleson F. B. 
Published: February 2007

AbstractChromosome aberrations (CA), micronuclei (MN, cytokinesis‐block [CB] method), and sister‐chromatid exchanges (SCE) were analysed in blood lymphocytes of 17 workers and 17 control subjects. The mean urinary mandelic acid level (average 9.4 mmol/1) and styrene glycol in blood (average 2.5 μmol/1) implied exposure to about 300 mg/m3 of styrene in the plant. The number of CA was significantly higher in non‐smoking workers compared with nonsmoking controls. A significant correlation was observed between duration of exposure and individual CA level of all workers. No significant effects were observed in MN or SCE. Single‐strand breaks (SSB) in DNA of isolated lymphocytes were studied in nine of the workers and eight of the controls by the DNA‐unwinding technique. The results showed an increase in SSB among the exposed workers. The present findings support earlier reports on the increase of structural CA in blood lymphocytes of workers in the reinforced plastic industry, and also show that SSBs are elevated in such workers.
Mutagenicity of n‐ and o‐acetyl derivatives of methyl 3,4‐diphenyl‐5‐hydroxylamino‐2‐furoate and n‐hydroxy‐4‐aminobiphenyl in salmonella typhimurium
Authors: Swaminathan Santhanam , Hatcher James F. , Bryan George T. , Yamamoto Katsumi , Tanaka Akira , Ichikawa Masataka , Snyder R. D. 
Published: February 2007

AbstractMethyl 3,4‐diphenyl‐5‐hydroxylamino‐2‐furoate (N‐OH‐MDPF) (I), methyl 3,4‐diphenyl‐5‐acetoxyamino‐2‐furoate(N‐OAc‐MDPF) (II), methyl 3,4‐diphenyl‐N‐hydroxy‐5‐acetylamino‐2‐furoate (N‐OH‐MDPAF) (III), and methyl 3,4‐diphenyl‐N‐acetoxy‐5‐acetylamino‐2‐furoate (N‐OAc‐MDPAF)(IV) were synthesized and tested for mutagenic activity for Salmonella typhimurium TA98 and TA100. The hydroxylamine (I) and acetyl derivatives (II–IV) did not show mutagenic activity in TA98 or TA100. In constrast, the parent nitro compound, methyl 3,4‐diphenyl‐5‐nitro‐2‐furoate (MDPNF) (V) was found to be equally active in TA98 and TA98‐DNP, and more active in TA100 and TA104. The mutagenic activity in TA100 and TA104 decreased significantly under anaerobic conditions. Additionally, MDPNF was previously shown to be less mutagenic in the nitroreductase‐deficient derivatives TA100NR and TA98NR, suggesting a requirement for nitro reduction. Incubation of V with NADPH and bacterial lysates of TA98 or TA98NR yielded a metabolite which was identified as I based on chromatographic and mass spectral character‐istics. The rate of reduction by the lysate of TA98NR was about one‐third that of TA98, showing a correlation between mutagenicity and nitroreductase activity. The lysates of TA98 did not reduce N‐OH‐MDPF further to the amine. In contrast to the lack of mutagenic activity of I–IV, N‐hydroxy‐4‐aminobiphenyl (N‐OH‐ABP) and its acetyl derivatives were active in TA98, but less so in TA98‐DNP. These data suggest that mechanisms involving O‐acetylation of N‐hydroxylamine to the acetoxyamine or acyl transfer reactions are not involved in the generation of mutagen from MDPNF. Furthermore, the differential mutagenic response of V in TA98 and TA98NR, its reduction to I, and the lack of activity of I suggest that the intermediates of reduction between the nitro and hydroxylamine, such as nitro or nitroso free radical anions, may be involved in mutagenesis. The decreased response of V under anaerobic conditions and increased response in TA104 suggest that secondary oxygen radicals generated from reduction intermediates may be responsible for the mutagenicity of MDPNF.
Mutagenicity in salmonella and sister chromatid exchange in mice for 1,4‐, 1,3‐, 2,4‐, and 3,4‐dimethylphenanthrenes
Authors: Sinsheimer J. E. , Giri A. K. , Hooberman B. H. , Jung K.‐Y. , Gopalaswamy R. , Koreeda M. , Brockman H. E. 
Published: February 2007

AbstractThe mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone‐marrow cells of mice was determined for 1,4‐, 1,3‐, 2,4‐, and 3,4‐dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4‐DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10‐diol formation.
Host cell reactivation of sunlamp‐exposed adenovirus in fibroblasts from patients with bloom's syndrome, ataxia telangiectasia, and huntington's disease
Authors: Rainbow Andrew J. , Skopek T. R. 
Published: February 2007

AbstractIn this study, a sensitive host cell reactivation (HCR) technique was used to examine the repair capacity for DNA damaged by sunlamp exposure in fibroblast strains derived from 5 normal individuals and 8 patients representing three different diseases associated with DNA repair deficiencies. Adenovirus type 2 (Ad 2) was exposed to radiation from a GE 275 W sunlamp and subsequently used to infect fibroblast monolayers. At 48 hr after infection, cells were scored for the presence of viral structural antigens (Vag) using indirect immunofluorescent staining. Previous reports using this technique showed a substantial reduction in the HCR of sunlamp‐exposed Ad 2 for infection of excision repair deficient fibroblasts from patients with xeroderma pigmentosum. In contrast, the HCR of Vag synthesis for sunlamp‐exposed Ad 2 was in the normal range for the three ataxia telan‐giectasia, three Bloom's syndrome, and two Huntington's disease fibroblast strains.
Mutagenicity of 3‐chlorodibenzofuran and its metabolic activation
Authors: Matsumoto Michi , Ando Mitsuru , Mortelmans K. E. 
Published: February 2007

Abstract3‐Chlorodibenzofuran was the only markedly mutagenic isomer among the four monochlorodibenzofurans. Although it was mutagenic even in the absence of 9,000g supernatant fraction (S9) of rat liver, it was further activated by the addition of S9. Metabolic activation of this compound in mutagenicity was studied using liver S9s and cell fractions which were prepared from rats treated with two inducers. 1,1‐Dichloro‐2,2‐bis(p‐chlorophenyl) ethylene (DDE) was used as an inducer of phenobarbital inducible cytochrome P‐450, and β‐naphthoflavone (βNF) was used as an inducer of 3‐methylcholanthrene inducible cytochrome P‐448. S9, microsomal, mitochondrial, and cytosolic fractions were obtained from four groups of rats, i.e., untreated, DDE treated, βNF treated, and DDE and βNF treated groups.Mutagenicity was tested using Salmonella typhimurium tester strain TA98, because this strain is more sensitive to 3‐chlorodibenzofuran than strain TA100. This experiment showed that 3‐chlorodibenzofuran was activated most highly by βNF‐induced microsomes. However, it was also activated by the cytosolic fraction. Moreover, it was highly activated in rat livers which were not treated with inducers. The activity of aryl hydrocarbon hydroxylase (AHH) of each fraction was measured. AHH did not always become an index of the metabolic activation of 3‐chlorodibenzofuran.This study showed that 3‐chlorodibenzofuran is activated not only by cytochrome P‐448, which is induced by 3‐methylcholanthrene type inducers, but also by the enzymes existing in normal rat liver. This result suggests a risk of manifestation of its toxicity to normal animals.
Activity of the human carcinogen meccnu in the mouse bone marrow micronucleus assay
Authors: Tinwell H. , Ashby J. , Littlefield L. G. 
Published: February 2007

AbstractThe nitrosourea mustard MeCCNU is the most recent organic chemical to be classified as a human carcinogen by IARC. MeCCNU gave a strong positive response when tested in the mouse bone marrow micronucleus assay. Activity was evident using either ip injection or oral gavage of the test chemical. These results further support the correlation between human carcinogens and their genotoxicity.
Micronuclei in mouse skin cells following in vivo exposure to benzo[a]pyrene, 7,12‐dimethylbenz[a]anthracene, chrysene, pyrene and urethane
Authors: He Shuilin , Baker Robert , MacGregor J. T. 
Published: February 2007

AbstractDetection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis‐blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 2.56 μg (10 nmol) 7,12‐dimethylbenz[a] anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12–24 hr after topical administration (79–88 MN/1,000 cells compared with 10–16 MN/1,000 cells in acetone‐treated controls). Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time of 24 hr was adopted for all test substances. Dose‐dependent increases in MN were observed with DMBA, benzo[a]pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study (0.128, 0.5, 50, and 50 μg, respectively). Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 μg to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes. The available data suggest that MN induction may be a useful indicator of the carcinogenic potential of chemicals applied to the skin.
Metabolism of 1,4‐dinitro‐2‐methylpyrrole, a mutagen formed by a sorbic acid‐nitrite reaction, by intestinal bacteria
Authors: Shu Yue‐Zhong , Kingston David G. I. , Van Tassell Roger L. , Wilkins Tracy D. , Rosenkranz H. S. 
Published: February 2007

Abstract1,4‐Dinitro‐2‐methylpyrrole (DNMP), a mutagenic product formed by the interaction of two common food additives, sorbic acid and sodium nitrite, was transformed to 1‐nitro‐2‐methyl‐4‐aminopyrrole (NMAP) by human fecal mixtures and various intestinal bacterial strains. Under anaerobic conditions the cell suspensions of Actinomyces, Bacteroides, Clostridium, Eubacterium, Fusobacterium, and Peptostreptococcus spp. demonstrated the nitroreduction activity. Under aerobic conditions, only Actinomyces and Bacteroides spp. showed activity, and this was at a decreased level. In cell suspensions of Bacteroides thetaiotaomicron VPI 5482, NAD(P)H and glucose accelerated the reduction rate, whereas dicoumarol and heat significantly inhibited the rate, and flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) did not affect the rate. With cell‐free preparations of the same strain, reduction required NAD(P)H as a cofactor in a dose‐dependent fashion and was inactivated by air and heat.
Seasonal indoor radon variations related to precipitation
Authors: Mose Douglas G. , Mushrush George W. , Chrosniak Charles E. , Morgan W. F. 
Published: February 2007

AbstractIndoor radon concentrations show a strong dependence on weather. Winter tends to be associated with higher than average indoor radon, and summer with lower than average. However, in northern Virginia, the summer of 1988 was wetter than the summer of 1987. Consequently, the regional indoor radon during the summer of 1988 was about 30% higher than during the summer of 1987, and indoor radon during the summer of 1988 actually exceeded the indoor radon level of the 1987–1988 winter.
Cytosine arabinoside enhancement of gamma irradiation induced mutations in human t‐lymphocytes
Authors: O'Neill J. P. , Sullivan L. M. , Hunter T. C. , Nicklas J. A. , Landolph J. R. , Hoffman G. R. 
Published: February 2007

AbstractThe frequency of 6‐thioguanine resistant (TGr) mutants induced in human G0 phase T‐lymphocytes by 200 cGy of gamma irradiation is greatly enhanced by incubation with cytosine arabinoside (ara‐C) after irradiation. The mutant frequency increased with increasing incubation time in ara‐C for up to 2 hr. This mutation induction required a phenotypic expression time of 5–8 days mass culture growth, similar to that found with mutants induced by 300 cGy of irradiation alone. Southern blot analysis of 40 isolated mutant clones revealed 8 independent mutations by T‐cell receptor (TCR) gene rearrangement patterns. Four of these eight showed hprt gene structural alterations (0.50). An alternative method to allow phenotypic expression was developed to minimize the isolation of hprt/TCR sibling mutants. The use of in situ expression in the microtiter dish wells resulted in the isolation of 17 independent mutations in 19 mutant clones. Ten of these 17 mutations showed hprt structural alterations (0.59). The high fraction of mutations involving structural alterations detected by Southern blot analysis is consistent with the known induction of chromosome aberrations by irradiation plus ara‐C treatment. We propose that both the increase in Mf and the increase in the incidence of hprt gene structural alterations are due to the accumulation of strand breaks in repairing regions of DNA under these conditions of ara‐C induced inhibition of repair. We further propose that upon release of the ara‐C inhibition, these repairing regions can interact to yield both gene mutations and chromosome aberrations.
Correlations between urinary nicotine or cotinine and urinary mutagenicity in smokers on controlled diets
Authors: Rahn Carolyn Anise , Doolittle David J. , Howard George , Riccio Ed , Nestman E. R. 
Published: February 2007

AbstractCigarette smokers have been reported to void urine that is more mutagenic, as measured in the Salmonella/microsome assay, than urine voided by nonsmokers. Several previous studies have attempted to correlate indices of tobacco smoke exposure (e.g., nicotine, cotinine, tar intake) with urinary mutagenicity, with conflicting results. These studies generally involved small numbers of smokers and did not carefully control diet, which is known to affect urinary mutagenicity markedly. Our objective was to conduct a controlled study to determine clearly if there were a correlation between urinary nicotine, cotinine, or nicotine + cotinine and urinary mutagenicity and to determine if nicotine or its major metabolite plays a role in the mutagenicity of urine from cigarette smokers. We used a large number of smokers (31), each of whom smoked both a tobacco‐burning cigarette and a tobacco‐heating cigarette on consecutive weeks, and we prepared and served identical diets to all subjects. Nicotine and cotinine concentrations were determined in small aliquots from urine samples collected over 24 hr, and the remaining urine sample was extracted and concentrated on XAD‐2 resin for mutagenicity assays in the Salmonella/microsome test. Nicotine, cotinine, and nicotine + cotinine were statistically correlated with mutagenicity of urine from smokers of the tobacco‐burning cigarette, but there was no correlation between nicotine, cotinine, or nicotine + cotinine and mutagenicity of urine from smokers of the tobacco‐heating cigarettes. Thus, although urinary nicotine and cotinine concentrations correlate with urinary mutagenicity in smokers of tobacco‐burning cigarettes, the present results indicate that nicotine and its metabolite are not responsible for the mutagenicity of smokers' urine.
Genotoxicity of multifunctional acrylates in the salmonella/mammalian‐microsome assay and mouse lymphoma tk+/−assay
Authors: Cameron Thomas P. , Seifried Harold E. , Rogers‐Back Andrea M. , Lawlor Timothy E. , Harbell John W. , Dunkel Virginia C. , Skopek E. R. 
Published: February 2007

AbstractMultifunctional acrylates are being used increasingly as replacements for solvents, and occupational and general population exposure to this structural class is expanding. Four multi‐functional acrylates and acrylic acid were tested for mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK+/−assays. In the Salmonella assay, two of the compounds (trimethylolpropane triacrylate and trimethylolpropane trimethacrylate) showed weakly positive results with a single tester strain (TA1535) in the presence of hamster liver S9; the other three compounds were negative. All five compounds were negative in the Salmonella assay without S9 activation. In the mouse lymphoma assay, two of the compounds (acrylic acid and ethylene glycol diacrylate) were positive in both the presence and the absence of S9, one compound was positive only in the presence of S9 (ethylene glycol dimethacrylate), and one compound was positive only in the absence of S9 (trimethylolpropane triacrylate).