bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photochemical formation of mutagenic compounds from alkenes and ozone or nitrogen dioxide
Authors: Victorin Katarina , Ståhlberg Margareta 
Published: February 2007

AbstractIn order to investigate the possible formation of mutagenic compounds from alkenes emitted in ambient air, laboratory experiments were performed with Salmonella typhimurium strain TA100 in a small‐scale flow‐through exposure system. The reaction time for mixtures of alkenes with ozone or nitrogen dioxide was 40 minutes, and the exposure time for bacteria was 6 hours. Ozone gave rise to a small mutagenic effect in combination with 1,3‐butadiene or vinyl chloride, with and without ultraviolet (UV) irradiation, but not in combination with ethene or propene. Nitrogen dioxide gave rise to a mutagenic effect in combination with propene, 1,3‐butadiene, or vinyl chloride, but only after UV irradiation. The mutagenic activity was highest with butadiene and seemed to be dose‐related to the concentration of nitrogen dioxide. Nitrogen dioxide with ethene did not produce a mutagenic effect. A mixture of ethene, propene, and butadiene, tested with ozone or nitrogen dioxide with UV irradiation, did not potentiate each other's mutagenic effect.
Metabolism of 2‐acetylaminofluorene in the chinese hamster ovary cell mutation assay
Authors: Heflich Robert H. , Casciano Daniel A. , Zhuo Zhou , Djurić Zora , Fullerton Nancy F. , Beland Frederick A. 
Published: February 2007

AbstractChinese hamster ovary (CHO) cells were exposed to 2‐acetylaminofluorene (2‐AAF) and 2‐aminofluorene (2‐AF), and several of their N‐oxidized metabolites in order to study the mechanisms by which arylamides and arylamines produce mutations in mammalian cells. The number of mutations induced at the hypoxanthine‐guanine phosphoribosyl transferase locus by each compound (mutants/106 CHO cells/nmol compound/ml) was estimated to be: N‐acetoxy‐2‐AAF, 310; N‐hydroxy‐2‐AF, 3; N‐hydroxy‐2‐AAF (with and without hepatic S9 activation), 0.7; 2‐AAF (with S9), 0.1; and 2‐AF (with S9), 0.09. With each compound, DNA adducts were also identified and quantified, and in all cases the major adduct was N‐(deoxyguanosin‐8‐yl)‐2‐AF. 2‐AAF and N‐hydroxy‐2‐AAF also formed minor amounts of N(deoxyguanosin‐8‐yl)‐2‐AAF and 3‐(deoxyguanosin‐N2‐yl)‐2‐AAF. The relationship between mutation induction and adduct formation for each of the derivatives was similar to that previously reported for N‐hydroxy‐2‐AF. Inclusion of the deacetylase inhibitor, paraoxon, reduced the mutagenicity of 2‐AAF, N‐hydroxy‐2‐AAF and N‐acetoxy‐2‐AAF, and the DNA adducts produced by N‐acetoxy‐2‐AAF to background levels. Acetyl coenzyme A increased the mutations and CHO cytosol‐mediated DNA binding of N‐hydroxy‐2‐AAF, but did not substantially increase these responses from N‐hydroxy‐2‐AF. N‐Hydroxy‐2‐AAF was not detectably metabolized by CHO cells. Taken together, these data indicate that CHO cells metabolized N‐acetoxy‐2‐AAF to a reactive derivative by N‐deacetylation to N‐acetoxy‐2‐AF, while N‐hydroxy‐2‐AF reacted direcitly with DNA. The major pathway of N‐hydroxy‐2‐AAF activation appeared to be an initial O‐acetylation to N‐acetoxy‐2‐AAF and this occurred to only a limited extent in the CHO cells. N‐Hydroxy‐2‐AAF also seemed to form an additional unknown ester intermediate that gave rise to acetylated DNA adducts. The limited O‐acetylase activity in CHO cells appeared to cntribute to the low sensitivity of these cells toward mutation induction by arylamines and arylamides.
Comparative mutagenicity of nine brands of coffee to salmonella typhimurium TA100, TA102, and TA104
Authors: Shane Barbara S. , Troxclair Alice M. , McMillin Debra J. , Henry Charles B. 
Published: February 2007

AbstractNine coffee preparations, four caffeinated instant brands, three caffeinated drip coffees, and two decaffeinated coffees, one of which was an instant brand, were evaluated for mutagenicity by the Ames assay using Salmonella typhimurium TA100, TA102, and TA104. All the coffees contained direct‐acting mutagens, which reverted the three strains. The inclusion of a rat microsomal enzyme preparation reduced the mutagenic response of the three strains in the presence of some of the coffee samples. Both glyoxal and methylglyoxal, 1,2‐dicarbonyls found in the coffees were mutagenic. The concentration of glyoxal, methylglyoxal, diacetyl, and guiacol were measured by gas chromatography/mass spectrometry. Caffeine, furfural, and 5‐methylfurfural concentrations were determined by high performance liquid chromatography. Although lower concentrations of methyglyoxal were found in the drip caffeinated coffees, the mutagenic potency of these preparations was higher than the instant coffees on a weight basis especially when TA104 was the indicator organism. Our findings agree with those of other workers who have shown that carbonyl compounds, which were present in all the brands tested, are partially responsible for the mutagenic response of coffee but that additional mutagens are also present.
Mutagenic potency of chlorofuranones and related compounds in salmonella
Authors: Ishiguro Yasuhisa , Santodonato Joseph , Neal Michael W. 
Published: February 2007

AbstractOne of the mutagenic byproducts associated with chlorinated humic waters and kraft pulp bleaching effluents was recently identified as 3‐chloro‐4‐(dichloromthyl)‐5‐hydroxy‐2(5H)‐furanone. This compound and several related chlorofuranones and precursors were synthesized and evaluated for direct‐acting mutagenicity in Salmonella typhimurium tester strain TA100. Mutagenicity was greatest for 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone, its 5‐methoxy derivative, and the precursor in their synthesis, 3‐(dichloromethyl)‐2,4,4‐trichloro‐2‐butenoic acid. Several of the compounds were tested in the presence of added rat liver homogenate S9 fraction, and in all cases mutagenicity was substantially reduced. An important structural feature which may govern the mutagenic response in these instances appears to be the cis arrangement of CHCl2 and Cl substituents on a carbon‐carbon double bond. These compounds may also be transformed in vitro to the same acyclic chlorine substituted alpha, beta‐unsaturated aldehyde derivative, which is proposed to be the agent responsible for the observed mutagenicity.
Chromosomal aberrations in the cotton rat, sigmodon hispidus, exposed to hazardous waste
Authors: Thompson Ruth A. , Schroder Gene D. , Connor Thomas H. 
Published: February 2007

AbstractThe study of chromosome damage in rodents living on hazardous‐waste sites may provide evidence of important biological consequences of chronic exposure to toxic chemical wastes. This study compared bone‐marrow cells of animals (Sigmodon hispidus) taken from two superfund waste‐disposal sites with those from an uncontaminated site and demonstrated that both populations exposed to hazardous wastes had significantly more structural and numerical aberrations than the control population.
Detection of carcinogenic glutamic acid pyrolysis products in worcestershire sauce by high‐performance liquid chromatography
Authors: Manabe Shigeo , Kanai Yoshikatsu , Yanagisawa Hiroyuki , Tohyama Kazuhiko , Ishikawa Shinsuke , Kitagawa Yasuhisa , Wada Osamu 
Published: February 2007

AbstractCommercially available Worcestershire sauce was analyzed for mutagenic and carcinogenic glutamic acid pyrolysis products using high‐performance liquid chromatography. These carcinogenic heterocyclic amines were found to be present in all brands of Worcestershire sauce analyzed. The identity of the carcinogens was confirmed by spectrometric analyses and the SOS umu‐test. The concentrations of 2‐amino‐6‐methyldipyrido[l,2‐a:3′,2′‐d]imidazole (Glu‐P‐1) and 2‐amino‐dipyrido‐[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐2) in the Worcestershire sauce were 695 ± 329 pmol/liter (mean ± SD, n = 5) and 1,839 ± 1,321 pmol/liter (n = 5), respectively.
Human mutagens: Evidence from paternal exposure?
Authors: Narod Steven A. , Douglas George R. , Nestmann Earle R. , Blakey David H. 
Published: February 2007

AbstractThe importance of inherited mutations as a cause of human disease has been established clearly through examples of well‐defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subsequent generations of persons exposed. The present lack of direct evidence for induced inherited genetic disorders in human beings hampers the development of risk estimation techniques for extrapolation from animal models. The most extensive prospective epidemiologic studies of inherited genetic effects have involved survivors of atomic bomb detonations and patients treated with cancer chemotherapy. In neither case has a significant elevation in inherited genetic effects or cancer been detected in the offspring of exposed individuals. Epidemiologic studies of subjects receiving chronic exposure may be confounded by the effect of maternal exposure during pregnancy. Consideration of only paternal exposure can minimize the confounding influence of teratogenicity, enhancing the resolving power of studies for inherited effects. Using this approach, retrospective (case‐control) studies of childhood cancer patients have provided limited but suggestive evidence for inheritance of induced effects. Endpoints, such as congenital malformations and spontaneous abortion following paternal exposure, can also be considered as indicators of heritable mutagenic effects. For example, there is limited evidence suggesting that paternal exposure to anaesthetic gases may cause miscarriage and congenital abnormalities as a result of induced male germ cell mutations. By comparing male‐exposure endpoints for which there are human data, as described above, with parallel or similar animal endpoints, such as dominant lethal, inherited cancer and “male teratogenic” effects, it is possible that suitable models for extrapolating to human risk can be developed. In order to establish a clearer relationship between induced mutation and genetic disease, the current surveillance systems should be expanded to include endpoints relevant to genetic study. The relaxation of regulations regarding access to census data could improve the chances of documenting such an association.
Utility of short‐term tests for genetic toxicity in the aftermath of the NTP's analysis of 73 chemicals
Authors: Brockman Herman E. , Demarini David M. 
Published: February 2007

AbstractThis manuscript has been reviewed by the Health Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
Different mutational profiles induced by N‐nitroso‐N‐ethylurea: Effects of dose and error‐prone DNA repair and correlations with DNA adducts
Authors: Zielenska M. , Guttenplan J. B. , Beranek D. 
Published: February 2007

AbstractThe DNA adducts and mutational profile produced by N‐nitroso‐N‐ethylurea (ENU) in Salmonella are examined. The adduct profile produced by ENU in isolated DNA and at two doses in Salmonella were similar, with one exception: O6‐ethylguanine (O6‐EtG) was not detected at the low dose in Salmonella. This adduct was presumably repaired by a constitutive repair system. The premutagenic adducts, O2‐ethylthymidine (O2‐EtdT) and O4‐ethylthymidine (O4‐EtdT) were detected, with the former adduct present at higher levels. The mutational profile was also determined at the same doses by utilizing a system involving a series of histidine auxotrophs of Salmonella with differing mutagenic specificities and a further subclassification of the revertants. Four different patterns of mutagenesis were observed; these were dependent on dose and on the presence or absence of the plasmid pKM101. The mutational spectrum produced at the higher dose in strains without the plasmid consisted mainly of GC→AT transitions. At the high dose, in strains harboring pKM101, three base changes contributed importantly to the mutational spectrum: GC→AT, AT→GC, and AT→CG. At the low dose in the strains without pKM101, little mutagenesis was observed, and in strains containing pKM101, mutagenesis was greatly enhanced with the most frequent mutations resulting from AT→GC and AT→CG base changes. O6‐EtG was presumably responsible for the bulk of the GC→AT transitions at the high dose. Calculations and evidence are presented indicating that O2‐EtdT is responsible for at least some of the mutagenesis that occurs at AT base pairs. O4‐EtdT and O2EtdT are probably responsible for a major fraction of the AT→GC transitions, and we suggest that error‐prone repair activity acting on O2‐EtdT and/or 04‐EtdT results in the AT→CG transversions.
DNA precipitation assay: A rapid and simple method for detecting DNA damage in mammalian cells
Authors: Olive Peggy L. 
Published: February 2007

AbstractWhen mammalian cells are lysed in 2% sodium dodecyl sulphate detergent followed by addition of an equal volume of 0.12 M potassium chloride, a precipitate forms that can be collected by low‐speed centrifugation. This precipitate contains the cell protein and nucleic acid in close association with protein. In die absence of DNA damage, most of the DNA precipitates, but when DNA strand breaks are created by exposing cells to ionizing radiation or toxic chemicals, DNA is released from the protein and remains in the supernatant after centrifugation. The proportion of DNA remaining in the supernatant is thus a measure of the amount of DNA damage. This assay is characterized in terms of optimum cell number and pH and dose‐response curves for DNA damage and cell survival following ionizing radiation, MNNG, BCNU, and VP‐16 are shown. Sensitivity, simplicity, speed, and large sample handling capacity should allow wide application of this new assay to a variety of questions concerning DNA damage and repair.
Chromosome aberration and sister chromatid exchange tests in chinese hamster ovary cells in vitro: II. Results with 20 chemicals
Authors: Loveday K. S. , Lugo M. H. , Resnick M. A. , Anderson B. E. , Zeiger E. 
Published: February 2007

AbstractTwenty chemicals were tested for their ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (ABs) in cultured Chinese hamster ovary cells (CHO). These chemicals were tested with and without an added metabolic activation system (rat liver S9 fraction). Four chemicals were negative in both assays, 1 induced ABs only, and 15 were positive for SCEs; 6 of these 15 also induced ABs.The effect of cell harvest time on the ability to detect the induction of chromosomal aberrations was examined for six chemicals. Five of these had caused at least one of the following: cell cycle delay, aberrations observed in first division metaphase cells in the SCE assay, or a weak response in the standard AB assay (10–12‐hr growth period). Three chemicals, chlorinated tri‐sodium phosphate, 1, 2‐dibromo‐3‐chloropro‐pane, and tetrakis(hydroxymethyl)phosphonium chloride, were positive using both the standard and extended harvest times. N‐Nitrosodimethyl‐amine and diphenhydramine HCI were only positive using an extended harvest time, and malo‐naldehyde was negative using both standard and extended harvest times.
Mutagenicity and induction of sister chromatid exchange by optically active enantiomers of secondary butyl methanesulfonate
Authors: Ball James C. , Salmeen Irving T. , Morris Suzanne M. 
Published: February 2007

AbstractThis report describes experiments in which a chiral alkyl methanesulfonate was used to investigate possible mechanisms by which alkylating agents cause their mutagenic, cytotoxic, and clastogenic effects. Optically active enantiomers and the racemic mixture of 2‐butyl methanesulfonate (2‐BMS) were cytotoxic and mutagenic in Chinese hamster V79 cells and in AS52 cells and mutagenic in Salmonella typhimurium strains TA100 and TA1535 (without the addition of exogenous metabolizing systems). Within the experimental uncertainties, the cytotoxicity and mutagenicity curves were the same for the R and S enantiomers and for the racemic mixture. The 2‐BMS isomers were cytotoxic and induced sister chromatid exchanges (SCE) in CHO‐K1‐BH4 cells. The cytotoxicity curve was similar to that observed with V79 and AS52 cells. The induction of SCE was linear between 1 and 6 mM 2‐BMS with no differences discernable between the isomers. The results can be interpreted two ways. The first interpretation is that 2‐BMS reacts via a carbocation, and the second interpretation involves an SN2 reaction of 2‐BMS with DNA. The latter interpretation suggests that the mechanisms of mutagenesis, cytotoxicity, or the induction of SCE cannot distinguish between small (four‐carbon) optically active DNA adducts. We favor the second interpretation because of solvolysis experiments showing the complete inversion of configuration of optically active 2‐octyl methanesulfonate (2‐OMS, Weiner and Sneen: J American Chemical Society 87:287–291, 1965). While we assume that optically active 2‐BMS will react using the same mechanism as chiral 2‐OMS, we cannot exclude the possibility that 2‐BMS reacts via a carbocation intermediate.
Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro III: Results with 27 chemicals
Authors: Gulati D. K. , Witt K. , Anderson B. , Zeiger E. , Shelby M. D. 
Published: February 2007

AbstractTwenty‐seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints (ABS and SCE) and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallyl phthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2, 4‐toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6‐ isomer; the mixture was carcinogenic, but the cytogenetic test results for the 2, 4‐ isomer were negative. Only six of the 27 chemicals tested produced an effect in one endpoint alone; the other 21 were either positive or negative for both ABS and SCE. Only one of the 27 chemicals tested required S9 for a positive response in the SCE test; two chemicals required S9 for a positive result in the ABS test. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest.
Sister chromatid exchanges induced by tertiary butyl hydroquinone in bone marrow cells of mice
Authors: Mukherjee Anita , Talukder Geeta , Sharma Archana 
Published: February 2007

AbstractTertiary butyl hydroquinone (TBHQ)—a phenolic antioxidant, was evaluated by assessing the induction of sister chromatid exchanges (SCEs) in bone marrow metaphase cells of mice. Six concentrations, 0.5, 2, 20, 50, 100, and 200 mg/kg, of TBHQ were injected intraperitoneally. A positive dose‐response effect in the SCE frequency was observed using the Cochran‐Armitage trend test. Two mg/kg of TBHQ was found to be the minimum effective dose. Study of the cell‐cycle kinetics showed a delay in cell cycle induced by the higher concentrations of TBHQ. Thus, TBHQ was found to be a DNA damage‐inducing agent and also a cytotoxic chemical in vivo in mice.
Pretreatment with mixed‐function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay
Authors: Shaddock J. G. , Heflich R. H. , McMillan D. C. , Hinson J. A. , Casciano D. A. 
Published: February 2007

AbstractA recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false‐negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ‐specific carcinogens. In this study, we examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed‐function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3′,4,4′‐tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measure of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4′‐Oxydianiline, 1‐nitropy‐rene, and TCAB produced concentration‐dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4′‐Oxydianiline and TCAB also induced a dose‐dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1‐nitropyrene was negative. 4,4′‐Methylenedianiline produced a marginal response, and 3,3′,4,4′‐tetrachloroazoxybenzene (TCAOB) was negative in Aroclor‐ and pheno‐barbital‐induced hepatocytes; however, TCAOB, as well as TCAB, produced concentration‐dependent increases in UDS in TCAB‐induced hepatocytes. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed‐function oxidase inducers.
Longitudinal study of the in vivo hprt mutant frequency in human T‐lymphocytes as determined by a cell cloning assay
Authors: O'Neill J. P. , Sullivan L. M. , Booker J. K. , Pornelos B. S. , Falta M. T. , Greene C. J. , Albertini R. J. 
Published: February 2007

AbstractThe in vivo frequency of mutants resulting from mutation at the hprt locus in human T‐lymphocytes can be determined by a cloning assay. This assay quantifies the frequency of 6‐thioguanine‐resistant (TGr) T‐cells through growth of colonies in 96‐well microtiter dishes. The reproducibility of the TGr mutant frequency values has now been assessed in a longitudinal study of six individuals (three male, three female, aged 22–33 years) employing 4–5 blood samples over a 26–37 week time period. Cloning assays were performed with both fresh and cryopreserved cell samples. No significant differences were found among the mutant frequency values for multiple samples from each individual with both fresh and cryopreserved cell samples. These results demonstrate the reproducibility of this cloning assay for in vivo mutant frequency determinations in human T‐lymphocytes.
Effect of erythropoietin on the micronucleus test
Authors: Suzuki Yuji , Nagae Yusuke , Ishikawa Tomoharu , Watanabe Yuzo , Nagashima Toshiharu , Matsukubo Kogen , Shimizu Hidesuke 
Published: February 2007

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 the rate of erythropoiesis in the bone marrow erythropoietin, a growth factor for the erythroblast, which was used to induce erythropoiesis.The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose‐response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1‐dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin. The effect of erythropoietin was maximal when erythropoietin was given 24 hr before DMH, indicating that accelerating the multiplication of erythroblasts will increase the frequency of micronuclei induced by mutagens.Induction of MPCE in the bone marrow by four other compounds—benzo(a)pyrene,2‐naph‐thylamine, mitomycin C, and vincristine—was also increased by pretreatment with erythropoietin.