bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutagenicity of some alkyl nitrites used as recreational drugs
Authors: Dunkel Virginia C. , Rogers‐Back Andrea M. , Lawlor Timothy E. , Harbell John W. , Cameron Thomas P. 
Published: February 2007

AbstractWhen the AIDS epidemic was in its earliest stages, and prior to identification of HIV as the etiological factor, the use of volatile nitrites by the male homosexual community to enhance sexual activities appeared to have a significant role in this disease. Preliminary observations indicated that that portion of the male homosexual community which developed Kaposi's sarcoma were also heavy nitrite users. These nitrites had been demonstrated to be mutagenic in bacteria and thus it was postulated that they could be responsible for the appearance of the sarcoma. To evaluate further the genotoxic activity of these chemicals, six nitrites, including those most commonly used by homosexuals for sexual gratification, were selected for testing in the mouse lymphoma TK +/− and Salmonella typhimurium mutagenicity assays. One chemical, n‐amyl nitrite, was negative in the mouse lymphoma assay, while the other five chemicals, n‐butyl, isobutyl, iso‐amyl, sec‐butyl, and n‐propyl nitrite, were positive. All six compounds were positive in the Salmonella assay. The mutagenic and known toxic effects of these chemicals remain a concern because a large population of teenagers and young adults continue to abuse these substances.
Genotoxicity studies with Cuman L in Drosophila melanogaster
Authors: Hemavathy K. C. , Krishnamurthy N. B. 
Published: February 2007

AbstractCuman L, a dithiocarbamate fungicide, was tested for its ability to induce sex‐linked recessive lethals (SLRLs) and II‐III chromosome translocations in Drosophila melanogaster by the larval feeding method. The three concentrations of Cuman L, of 20, 40, and 60 μl/100 ml, induced significant (P<0.01) increases in SLRLs but failed to induce any translocations.
Genotoxic activity of benomyl in different test systems
Authors: Georgieva V. , Vachkova R. , Tzoneva M. , Kappas A. , Morgan W. F. 
Published: February 2007

AbstractBenomyl (methyl‐1‐[butylcarbamoyl]‐2‐benzimidozole carbamate), a benzimidazole derivative fungicide, was tested in the Ames test for point mutations; in human lymphocyte cultures for cell division disturbances, chromosomal aberrations, and SCE; in rat bone marrow cells in vivo for micronuclei; and in rats in vivo for dominant lethals. Benomyl was negative in the Ames test. In human lymphocytes, benomyl at concentrations of 0.5, 1.0, and 2.0 μg/ml decreased the number of cells undergoing third division whereas at the concentrations of 0.25 to 4.0 μg/ml it strongly increased the number of aneuploid cells. Benomyl was also shown to induce sister chromatid exchanges and micronuclei but not chromosome aberrations. Benomyl decreased the number of female rats with implants but did not cause any dominant lethals.
Review of the mutagenicity of ethylene oxide
Authors: Dellarco Vicki L. , Generoso Walderico M. , Sega Gary A. , Fowle John R. , Jacobson‐Kram David , Brockman H. E. 
Published: February 2007

AbstractEthylene oxide has been shown to be on effective mutagen in a variety of organisms ranging from bacteria to mammalian cells. There is also an association between ethylene oxide exposure and human somatic cell cytogenetic damage. Furthermore, ethylene oxide has been shown to alkylate protein and DNA at exposure levels that have been encountered occupationally. Ethylene oxide is not only effective at producing somatic cell mutations but also at inducing genetic damage in germ cells. While it is clear that ethylene oxide is a germ cell mutagen in whole mammals, the mechanism(s) by which it produces genetic lesions in germ cells is uncertain.
Induction of gastrointestinal tract nuclear anomalies in b6c3f1 mice by 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2[5h]‐furanone and 3,4‐(dichloro)‐5‐hydroxy‐2[5h]‐furanone, mutagenic byproducts of chlorine disinfection
Authors: Daniel F. B. , Stober J. A. , Olson G. R. , Galloway S. M. 
Published: February 2007

AbstractTwo chlorinated hydroxylated furanones, 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2[5H]‐furanone (MX) and 3,4‐(dichloro)‐5‐hydroxy‐2[5H]‐furanone (MA), are bacterial mutagens and they are also byproducts of chlorine disinfection, and frequent contaminants of drinking water. In this work MX is shown to induce nuclear anomalies in the gastrointestinal tract of the B6C3F1 mouse. The other chlorohydroxy‐furanone, MA, gives suggestive evidence of activity. In this bioassay MX was approximately equivalent in potency to epichlorohydrin (ECH) but was much less potent than methylnitrosourea (MNU). The latter two chemicals are confirmed rodent gastrointestinal tract carcinogens. The duodenum was the most sensitive tissue responding with both increased numbers of nuclear anomalies per mouse and increased incidence of animals presenting the nuclear aberrations 24 hr after a single oral dose of 0.37 mmol/kg−1 of MX. MA also induced a significant increase in duodenal nuclear anomalies, but only at the highest dose (0.46 mmol/kg−1). The proximal colon and fore‐stomach responded to MX but not MA. This is the first study demonstrating that chlorohydroxy‐furanones are capable of inducing nuclear toxicity in vivo. However, it is clear, for MX at least, that its potency in the gastrointestinal tract nuclear anomalies assay is not commensurate with its extreme bacterial mutagenicity. Since the gastrointestinal tract tissues are directly exposed to orally administered genotoxins, one possible explanation for the weak response observed in this study could be that mammalian cells can effectively detoxify chlorohydroxyfuranones.
Evaluation of the genotoxic potential of glutaraldehyde
Authors: Clair Mary Beth G. St. , Bermudez Edilberto , Gross Elizabeth A. , Butterworth Byron E. , Recio Leslie , Carrano A. V. 
Published: February 2007

AbstractThe cytotoxic and genotoxic effects of glutaraldehyde were studied in vitro in the human TK6 lymphoblast cell line and in primary cultures of rat hepatocytes. TK6 lymphoblasts were exposed to glutaraldehyde for 2 hr in serum‐free GSH‐free media. Cytotoxic effects were observed at concentrations as low as 10 μM with only 10% cell survival at 20 μM. Alkaline elution studies indicated that glutaraldehyde‐induced DNA‐protein crosslinking increased linearly over the concentration range from 0 to 25 μM. Glutaraldehyde‐induced mutations were assessed at the thymidine kinase locus over the same concentration range and reached a plateau at 10 μM of about six times the background mutant frequency. At equivalent levels of DNA‐protein crosslinks and cytolethality, glutaraldehyde was mutagenic at approximately a one‐seventh lower concentration than the rodent nasal carcinogen formaldehyde (Craft et al.; Mutation Research 176:147–155, 1987). Glutaraldehyde induced a marginal increase in unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay, but only at the two highest concentrations of 50 and 100 μM, indicating the induction of some DNA excision‐repair activity. These data demonstrate that glutaraldehyde exhibits DNA‐reactive genotoxic activity that may involve, at least in part, DNA‐protein crosslinking in these cell culture models. These findings suggest the need to examine the potential carcinogenic activity of glutaraldehyde in appropriate inhalation studies.
Mutagenicity of methylazoxymethanol acetate in the presence of alcohol dehydrogenase, aldehyde dehydrogenase, and rat liver microsomes in Salmonella typhimurium his G46
Authors: McMahon Timothy F. , Cunningham Michael L. , Prival M. J. 
Published: February 2007

AbstractMethylazoxymethanol (MAM) is the short‐lived toxic and carcinogenic aglycone of cycasin, a natural component of the cycad plant. In the present study, the stable acetate ester of MAM, MAM acetate, was tested in combination with porcine liver esterase and Salmonella typhimurium His G46 to study the comparative mutagenicity of this compound in the presence of rat hepatic alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and rat liver microsomes. In the presence of rat liver microsomes and an NADPH‐generating system, mutagenicity of MAM acetate was not significantly altered. However, addition of rat liver 105,000g supernatant fraction and/or NAD+ significantly increased the number of his+ revertants above control. A concentration‐dependent increase in mutagenicity of MAM acetate was observed for NAD+ from 50 to 200 μM, while NADP+ caused a decrease in mutagenicity of MAM acetate in this same concentration range. Pyrazole (100–500 μM) had no significant effect on mutagenicity of MAM acetate in the presence of rat liver 105,000g supernatant, while disulfiram at 500 μM resulted in a significant decrease in mutagenicity of MAM acetate. The results of this study implicate ALDH as essential in activation of MAM acetate to a mutagenic species in this system, while the role of ADH and microsomes appears to be minimal.
Micronuclei as an index of cytogenetic damage: Past, present, and future
Authors: Heddle J. A. , Cimino M. C. , Hayashi M. , Romagna F. , Shelby M. D. , Tucker J. D. , Vanparys Ph. , MacGregor J. T. 
Published: February 2007

AbstractThe workshop was designed to present what is known about the production of micronuclei, what protocols are now accepted or proposed internationally, what new results have been obtained, and what new methods and protocols are likely to be forthcoming. This report is designed to convey the flavour of the workshop and to provide the essence of the new information. After the workshop an effort was made to determine what single protocol would satisfy the requirements set for the micronucleus test by as many regulatory agencies as possible. The result, reported here, includes the requirements of six regulatory authorities in Canada, the European Economic Community, the Organization for Economic Co‐operation and Development, Japan, and the United States.
Induction of prophage lambda by chlorinated organics: Detection of some single‐species/single‐site carcinogens
Authors: Demarini David M. , Brooks Harold G. 
Published: February 2007

AbstractTwenty‐eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage‐induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage‐induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage‐induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage‐induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage‐induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single‐species, single‐site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage‐induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that does not revert the standard Salmonella tester strains.
Nitrobenzo[a]pyrene‐induced DNA amplification in SV40‐transformed chinese hamster embryo cells
Authors: Neft Robin E. , Roe Amy L. , Schol Henry M. , Fu Peter P. , Mittelstaedt Roberta A. , Casciano Daniel A. 
Published: February 2007

AbstractNitrobenzo[a]pyrenes (NBaPs) are ubiquitous environmental pollutants that produce mulations in Salmonella typhimurium and Chinese hamster ovary cells. In this study, 1‐, 3‐, and 6‐NBaP induced amplification of SV40 DNA sequences in an SV40‐transformed Chinese hamster embryo cell line which is sensitive to DNA amplification by various known carcinogens. Of the three isomers, 3‐NBaP produced the highest level of gene amplification, which was 4.8 relative to untreated controls at a dose of 5 μg/ml. Considering the relationship between gene amplification and tumorigenesis, it seems prudent to carry out a more exhaustive analysis of the carcinogenic potential of these agents.
Mutations in topA interfere with the inducible expression of DNA damage response loci in salmonella typhimurium
Authors: Smith C. Mark , Arany Zoltan , Orrego Cristian , Eisenstadt Eric 
Published: February 2007

AbstractStrains of Salmonella typhimurium deficient in topoisomerase I activity (topA mutants) are UV sensitive and non‐mutable (Overbye and Margolin: J Bacteriol 146:170–178, 1981). Using lac‐operon fusions to DNA damage inducible (din) loci we investigated whether these observations could be explained by an inability of topA strains to efficiently induce DNA damage responses. Mitomycin C (MMC)‐induced expression of lac‐operon fusions to uvrB and to a second SOS locus, din‐9, was largely eliminated in topA bacteria. The inducible expression of several other din‐fusions was also diminished. This inducibility defect was mimicked by growth of din‐9 topA+ bacteria in media of high osmolarity, a condition that leads to increased DNA supercoiling. Inhibitors of DNA gyrase efficiently induced din‐9 in topA bacteria. Together, these results suggest that the topA effect on din expression may be mediated at the level of DNA supercoiling. The sensitivities of a number of din‐fusions to topA paralleled the degree to which they were repressed by excess LexA, suggesting that mutations in topA might influence LexA‐operator interactions and/or increase lexA expression.
Evidence that inhibitor(s) are formed which may interfere with the growth of revertant colonies in the ames salmonella and the E. Coli tryptophan reverse mutation assays when strictly anaerobic conditions are used
Authors: Mortelmans Kristien , Cox Mike 
Published: February 2007

AbstractSpontaneous and chemically induced revertant colonies were not observed on plates when a strictly anaerobic environment and anaerobically prepared media were used to perform the Ames histidine reversion assay with each of eight different Salmonella strains. A similar effect was observed when the E. coli tryptophan reverse mutation assay was performed under strictly anaerobic conditions.We provide evidence here that under anaerobic conditions growth inhibitor(s) are formed by the S. typhimurium and E. coli bacteria when the limited histidine and tryptophan, respectively, are depleted from the medium. The inhibitor(s) are nonspecific and inhibit the growth not only of prototrophic bacteria but also of the inhibitorproducing bacteria as measured by neutralized supernatants of growth‐limiting minimal liquid cultures. Inhibitor(s) are also formed in stationary phase cultures of Salmonella and E. coli in minimal liquid medium supplemented with excess histidine and tryptophan, respectively. These results suggest that inhibitor formation under anaerobic conditions is a physiological phenomenon which interferes with at least two reverse mutation assays. Whether or not it also interferes with the reverse mutagenesis process remains to be determined. © 1992 Wiley–Liss, Inc.
Human HPRT mutant database: Software for data entry and retrieval
Authors: Cariello Neal F. , Craft Teresa R. , Vrieling Harry , Van Zeeland Albert A. , Adams Thomas , Skopek Thomas R. 
Published: February 2007

AbstractWe have developed a computer database containing information on over 1,000 human hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants. Both published and unpublished data are present. The database itself is maintained in a dBASE format (.DBF) and we provide a set of programs to examine and extract information from the database. A program to input information into the database is also supplied. The database and programs are available directly from us or via remote FTP (file transfer protocol) using BITNET/INTERNET. All programs require an IBM‐compatible computer, the MS‐DOS operating system (version 3.3 or greater), and a hard disk with about 5 megabytes of free disk space.The purpose of the database is 1) to allow investigators to contribute their HPRT mutants directly to the database in a standardized fashion, and 2) to allow access to the entire database with a set of programs that allows manipulation and extraction of data. For example, using our programs it is possible to i) order the database by base pair position, ii) examine only information regarding mutagenesis by a particular agent, iii) search for a particular author, iv) create a report which contains selected portions of the database, the report can be printed or saved as a file.The database will be updated every several months and distributed. © 1992 Wiley‐Liss, Inc.
Evaluation of the mutagenicity of an n‐nitroso contaminant of the sunscreen padimate O: N‐nitroso‐N‐methyl‐p‐aminobenzoic acid, 2‐ethylhexyl ester (NPABAO)
Authors: Dunkel Virginia C. , San Richard H. C. , Harbell John W. , Seifried Harold E. , Cameron Thomas P. 
Published: February 2007

AbstractThe nitrosamine contaminant, N‐nitroso‐N‐methyl‐p‐aminobenzoic acid, 2‐ethylhexyl ester (NPABAO), of the major sunscreen ingredient Padimate O (4‐N, N′‐dimethylamino‐benzoic acid, 2‐ethylhexyl ester) was synthesized and tested for mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK+/‐assays. In contrast to the previously reported positive responses in S. typhimurium tester strains TA100 and TA1535 [Loeppky et al., 1991], there were no increases in the number of revertants with strains TA98, TA100, TA1535, and TA1538 in either the Salmonella plate incorporation [Ames et al., 1975] or preincubation [Yahagi et al., 1977] assays. Additional testing with Salmonella, following the modified preincubation procedure [Rogan, 1990] that gave the initial positive response, was also negative. Data from the mouse lymphoma assays were also uniformly negative.During synthesis of NPABAO, small amounts of 4‐N, N'‐dimethylamino‐3‐nitrobenzoic acid, 2‐ethylhexyl ester (DMANBAO) can be formed. To determine whether the reported positive mutagenicity response of NPABAO could be the result of trace amounts of DMANBAO in the NPABAO, that compound was also synthesized and tested for mutagenicity with Salmonella. Positive responses were obtained with tester strains TA98 and TA 1538 but not with TA100 and TA1535, indicating that DMANBAO was not responsible for the increase in revertants originally reported. © 1992 Wiley‐Liss, Inc.
Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L.
Authors: Chulasiri Malyn , Bunyapraphatsara Nuntawan , Moongkarndi Primchanien 
Published: February 2007

AbstractStudies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 μg/plate, both compounds showed no mutagenicity and no cytotoxicity toward S. typhimurium strains TA98 and TA100 either in the presence or absence of S9 mix. However, these substances were antimutagens toward 2–aminoanthracene, aflatoxin Bl (in TA98), and dimethylnitrosamine (in TA100); but neither substance inhibited the direct mutagenic activity of 2‐(2‐furyl)‐3‐(5‐nitro‐2‐furyl) acrylamide nor that of sodium azide in strains TA98 and TA100, respectively. © 1992 Wiley‐Liss, Inc.
Japanese guidelines for mutagenicity testing
Authors: Sofuni Toshio 
Published: February 2007

AbstractSeveral Japanese agencies are required to perform mutagenicity tests according to regulatory guidelines. Although each agency's guidelines address a specific purpose, the experimental principles behind them are similar, and general methodological recommendations have been issued by the Ministry of Agriculture, Forestry, and Fisheries [1985]; Ministry of Health and Welfare [1990]; Ministry of Labor [1991]; and Ministry of Health and Welfare [1992]. Four major guidelines for mutagenicity testing in Japan and some amendments are briefly introduced. In addition, several procedures in Japanese guidelines that differ from those of other countries or organizations are discussed. © 1993 Wiley‐Liss, Inc. © 1993 Wiley‐Liss, Inc.
In vitro micronucleus bioassay of human peripheral lymphocytes for adriamycin in the presence of cyclophosphamide and urines of patients administered anticancer drugs
Authors: Boucher R. , Livingston G. K. , Hee S. S. Que 
Published: February 2007

AbstractThe aim of this study was to develop an in vitro human peripheral lymphocyte micronucleus bioassay involving phytohemagglutinin stimulant for urines containing adriamycin (ADR) and cyclophosphamide (CP). In vitro studies with defined concentrations of ADR, CP, and fresh urine showed that mitotic indices and micronuclei counts/1,000 cells had to be log (X + 1) transformed to be able to use parametric statistics and that a specific micronucleus assay for ADR in the presence of CP and urine for 5–15 ng ADR/mL had been developed. Whereas CP alone could be detected between 196–522 μg/mL, this effect was abolished in the presence of 15 ng ADR/mL. Interdonor variabilities relative to ADR sensitivity and CP linear dynamic range were marked, but intradonor variability was small. The MN bioassay tolerated < 10% urine. Results for urines from nine patients receiving antineoplastic drugs (CP, all; ADR, 3; 5‐fluorouracil, 3; methotrexate, 3; vincristine, 4; procarbazine, 1; and megestrol acetate, 1) showed that only 1/3 patients given ADR were detected, and two others not given ADR were positive. All frozen urines from the 12 control subjects and the nine patients exhibited depressed mitotic index, with, however, no control patient urines inducing increased micronuclei. Two patients had urines of undefined genotoxic potential since undepressed mitotic indices were not attainable by dilution. The effects of combination chemotherapy in addition to freezing and storage influences were complex. More research is required to be able to interpret the results. ©1993 Wiley‐Liss, Inc.
DNA damage, photorepair, and survival in fish and human cells exposed to UV radiation
Authors: Ahmed Farid E. , Setlow Richard B. , Grist Eleanor , Setlow Neva 
Published: February 2007

AbstractThe effect of various wavelengths of UVB radiation on the induction of cyclobutane pyrimidine dimers in fish cells and human fibroblasts and the repair of these lesions were studied using an UV‐endonuclease to measure dimers (endonuclease sensitive sites) by sedimentation of radioactive DNA, by gel electrophoresis of unlabeled DNA, and by cell survival. The data show that fish cells have an efficient photoreactivation system at wavelength > 304 nm that reverses cytotoxicity and dimer formation after exposure to filtered sunlamp irradiation of a shorter wave‐length (λ > 290 nm). Shorter wavelengths in UVB (<304 nm) are more effective in photoreversal than longer ones (<320 nm). As a consequence, 50–85% of dimers induced by these wavelengths in fish are photoreactivated while they are being formed. A major cytotoxicological lesion is the cyclobutane pyrimidine dimers. Cultured human fibroblasts do not possess such a repair system. These results indicate that sun‐lamp irradiation has wavelengths that both damage and repair DNA.