bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crotonaldehyde is mutagenic in Salmonella typhimurium TA100
Authors: Neudecker Tilman , Eder Erwin , Deininger Christoph , Henschler Dietrich 
Published: February 2007

AbstractThe mutagenicity of crotonaldehyde in Salmonella typhimurium TA100 cannot be demonstrated in the standard plate incorporation assay. However, as reported earlier by our group, this α,β‐unsaturated aldehyde is clearly mutagenic in the liquid assay modification of this testing procedure. Carried out because of the doubts recently expressed by Cooper et al. (Environ Mutagen 9:289–295, 1987) concerning the observed mutagenicity of crotonaldehyde in S. typhimurium TA100, this study confirms that this compound is clearly a direct (without activation by mammalian microsomes)‐acting mutagen in S. typhimurium TA100 under appropriate conditions in the preincubation assay. The observed mutagenicity is increased by extended preincubation time and increased bacterial cell densities.
Cytogenetic analysis of spontaneous and 2‐cyanoethylene oxide‐induced tk —/— mutants in TK6 human lymphoblastoid cultures
Authors: Kodama Yoshiaki , Boreiko Craig J. , Skopek Thomas R. , Recio Leslie 
Published: February 2007

AbstractTwo phenotypic classes of selectable tk —/— mutants have been isolated from the TK6 human lymphoblast cell line; one has a normal growth rate (tkn) relative to the parental cell line; the other has a slow growth rate (tks). Complete karyotypes of metaphase chromosomes were prepared and analyzed from 16 tks mutants (eight spontaneous and eight 2‐cyanoethylene oxide [CNEtO]‐induced), two spontaneous tkn mutants, and the parental TK6 cell line. Southern blot analysis of these tk —/— mutants indicated that all had lost a 14.8 kb polymorphic band corresponding to the active tk allele. No chromosome abnormalities with respect to the parental cell line TK6 were observed in eight spontaneous tks mutants. Chromosome abnormalities that may have been related to CNEtO treatment were observed in four of eight CNEtO mutants. However, chromosome 17, containing the tk locus in man, was cytologically normal with respect to the parental TK6 cell line in 15 of 16 tks mutants. A visible abnormality of chromosome 17 was present in one CNEtO‐induced tks mutant. The abnormality was a duplication of the long arm of the chromosome 17, with break points at q11 and q21. The latter break point is close to the site of the tk locus, suggesting that the aberration observed may be associated with tk —/— phenotype. These observations contrast with the relatively high incidence (>59%) of chromosome 11 abnormalities reported in tks (small colony) mouse lymphoma L5178Y/TK + / — mutants.
Chemical mutagenesis testing in Drosophila. VI. Interlaboratory comparison of mutagenicity tests after treatment of larvae
Authors: Valencia R. , Mason J. M. , Zimmering S. 
Published: February 2007

AbstractPrevious publications on the National Toxicology Program (NTP)‐sponsored mutagenicity testing program in Drosophila dealt with evaluations of chemicals following adult treatment (feed, injection). The current paper deals with a comparison between the laboratories at Brown University (BRU) and the University of Wisconsin at Madison (UWM) regarding the response of larvae to treatment with chemicals in the sex‐linked recessive lethal (SLRL) test and, where appropriate, the reciprocal translocation test as well. Dimethylnitro‐samine (DMN) and dimethylbenz(a)anthracene were used first as reference mutagens. Six coded compounds were then evaluated regarding their repeatability in the two laboratories; the compounds were benzo(a)pyrene, 3‐methylcholan‐threne, coumarin, quinoline, formaldehyde, and 9‐aminoacridine. It was concluded that at this time it would be imprudent to forgo larval treatment in cases where compounds proved negative after adult feeding. Accordingly, testing a series of 20 compounds negative after adult treatment is in progress.
Chemical mutagenesis testing in Drosophila. VII. Results of 22 coded compounds tested in larval feeding experiments
Authors: Zimmering S. , Mason J. M. , Valencia R. 
Published: February 2007

AbstractTwenty‐two chemicals were tested for mutagenicity in the sex‐linked recessive lethal (SLRL) mutation assay after being fed to Drosophila melanogaster larvae. One compound, maleic hydrazide, was found to be mutagenic. It was tested for the ability to produce reciprocal translocations (RTs) and was positive in that assay as well.
Biotesting of wastewater: A comparative study using the Salmonella and CHO assay systems
Authors: Waters L. C. , Schenley R. L. , Owen B. A. , Walsh P. J. , Hsie A. W. , Jolley R. L. , Buchanan M. V. , Condie L. W. 
Published: February 2007

AbstractMeans to assess the toxicity of wastewaters are essential to implementing the Federal Clean Water Act. Health risk assessment based on single chemicals is limited by the number of chemicals that can be identified and to those chemicals for which toxicity data are available. Long‐term whole animal tests on large numbers of waste‐water samples are not practical. In this study, two short‐term tests, the Salmonella mutagenicity assay and the Chinese hamster ovary (CHO) cell assay for mutagenicity and cytotoxicity, were evaluated as potentially useful biomonitors of wastewaters. Standard assay protocols were modified to allow testing of up to 2.5 and 3.4 ml of unconcentrated water in the bacterial and mammalian cell tests, respectively. Cytotoxicity and mutagenicity were detected in some unconcentrated wastewater samples using these modifications. Data on eight wastewater samples, representing five different sites, indicated that the Salmonella test is the more sensitive indicator of mutagenic activity in those samples, whereas the CHO test is a sensitive indicator of the presence of cytotoxic components. Wastewater concentrates, prepared by adsorption onto XAD‐2 and “blue cotton,” were compared in the two bioas‐says. In a single concentrate, the two short‐term tests detected distinctly different mutagens. Advantages of using the CHO‐AS52 cell line instead of the CHO‐K1BH4 line for detecting wastewater mutagens were indicated. This study illustrates the complementary use of multiple bioassays and concentration methods to detect and characterize toxic components in wastewater.
Induction of prophage lambda by chlorophenols
Authors: Demarini David M. , Brooks Harold G. , Parkes Douglas G. 
Published: February 2007

AbstractChlorinated phenols, which are used primarily as wood preservatives and fungicides, are present in most air, water, and soil samples in industrialized areas as well as in the urine of most people. We have examined the ability of phenol and the 19 isomers of chlorophenol to induce DNA damage using the Microscreen prophage‐induction assay in Escherichia coli. Seven of the isomers (2,3,4,‐tr, 2,4,5‐tri, 3,4,5‐tri, 2,3,4,5‐tetra, 2,3,6‐tri, 2,4,6‐tri, and pentachlorophenol) induced prophage lambda in the presence of S9, with the first three being ∼ 10 times more potent than the last three. The more potent isomers have either one or no chlorine atom ortho to the OH group; whereas the less potent isomers have two chlorine atoms ortho to the OH group. Although none of the 20 compounds is mutagenic in Salmonella, the prophage‐induction results agree with findings by others that most of these seven isomers are clastogenic, are associated with cancer and chromosomal aberrations in humans (pentachlorophenol), and are carcinogenic in radents (2,4,6‐tri and pentachlorophenol). A likely basis for the genotoxicity of the seven isomers involves the metabolism of the parent isomer to a chlorohydroquinone, which can form a chlorobenzosemiquinone in the presence of oxygen. These two metabolites can produce free radicals that can cause DNA strand breaks, resulting in prophage induction in E. coli or, possibly, the chromosomal aberrations/cancer associated with human exposure to chlorophenols.
LUMO Energies and hydrophobicity as determinants of mutagenicity by nitroaromatic compounds in Salmonella typhimurium
Authors: Lopez de Compadre Rosa L. , Debnath Asim Kumar , Shusterman Alan J. , Hansch Corwin 
Published: February 2007

AbstractQuantitative structure‐activity relationships have been derived for the mutagenic activity of 47 nitroaromatic compounds acting on Salmonella typhimurium (TA100) and 66 acting on TA98. The mutagenicity is linearly dependent on the energy of the lowest occupied molecular orbital and bilinearly dependent on the hydrophobicity (octanol/water log P) of the mutagens. The mechanism of action is considered in the light of these findings.
Urine mutagenicity and biochemical parameters as markers of exposure to petroleum pitch using a rat model
Authors: Pasquini R. , Monarca S. , Sforzolini G. Scassellati , Savino A. , Fatigoni C. , Puccetti P. 
Published: February 2007

AbstractA petroleum pitch sample collected in a carbon electrode factory was studied using a series of in vivo assays for genotoxicity and enzymatic induction capability. Rats were treated with the petroleum derivative in three doses: 100, 50, and 10 mg/kg body weight. The treatment produced a rapid excretion of mutagenic substances in the urines of the first 24 hr only in rats treated with high doses (100 and 50 mg/kg). No faecal mutagenic activity was observed. Analyses of urinary thioethers showed that urinary metabolites derived from the compounds present in the pitchsample at the lowest doseadministered (10 mg/kg) were eliminated primarily as cysteine conjugates. The pitch sample was found to be a good inducer of pulmonary and hepatic aryl hydrocarbon hydroxylase, especially after a 50 mg/kg dose. Urinary D‐glucaric acid content was always statistically increased in treated animals compared with controls, confirming the enzymatic induction activity. Hepatic glutathione‐S‐transferase activity increased following treatment with 50 and 10 mg/kg doses.
Genotoxic effects of five polycyclic aromatic hydrocarbons in human and rat mammary epithelial cells
Authors: Mane Suneeti S. , Purnell Dallas M. , Hsu Ih‐Chang 
Published: February 2007

AbstractFive polycyclic aromatic hydrocarbons (PAHs) of different carcinogenic activities were evaluated for their effects on DNA synthesis (3HTdR labeling index (L.I.)) of rat and human mammary epithelial cells (MEC) and for their effects on chromosomes in MEC‐mediated sister chromatid exchange (SCE) assays. When compared with DMSO‐treated cells, exposures of rat MEC to the two most potent carcinogens (5 μg/ml for 24 hr), i.e., 7,12‐dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B[a]P), resulted in a 45‐62% reduction in the L.I. of rat MEC. Another carcinogen, 20‐methylcholanthrene (MCA), produced a 35‐48% reduction in L.I., while the noncarcinogenic PAHs, 1,2‐benzanthracene (BA) and benzo(e)pyrene (B[e]P), showed no effect. Similarly, exposures of human MEC to DMBA and B[a]P resulted in a 50‐90% depression in L.I. while BA was significantly less effective (30% reduction). When cocultivated with Chinese hamster V‐79 cells in the presence of PAH,both rat and human MEC can activate and release the active metabolites to induce SCE in V‐79 cells. In the rat MEC‐mediated assay for all 5 PAHs, the frequencies of SCE per chromosome in DMBA‐, B[a]P‐, MCA‐, BA‐, B[e]P‐, and DMSO (solvent control)‐treated groups were 6, 3, 1.4, 0.7, 0.4, and 0.3, respectively. DMBA was most effective in increasing SCE, while B[e]P was ineffective. In the human MEC‐mediated assay, B[a]P was more effective than DMBA in inducing SCE, and the frequencies of SCE per chromosome were 4.5 and 3.6 in B[a]P‐ and DMBA‐treated groups, respectively. Comparing depression of L.I., SCE, and in vivo carcinogenecity for the 5 PAHs, SCE mediated by rat MEC is better correlated with carcinogenecity in rat than L.I. depression.
Comparison of three assays for genetic effects of antineoplastic drugs on cancer patients and their nurses
Authors: Krepinsky A. , Bryant D. W. , Davison L. , Young B. , Heddle J. , McCalla D. R. , Douglas G. , Michalko K. 
Published: February 2007

AbstractThree assays have been compared for their ability to detect genetic damage caused by antineoplastic drugs in cancer patients and possible damage in the nurses who administered these drugs. The assays were sister chromatid exchanges (SCE) and chromosomal aberrations in peripheral blood lymphocytes, and the Salmonella/mammalian microsome assay on urine. Three comparisons were made: 1) patients before versus after treatment; 2) the administering nurses immediately after their work period versus after a few days off that followed (work and off‐work); 3) the exposed nurses versus other nurses who did not administer antineoplastic drugs (controls).The SCE assay detected the treatments in all eight patients from whom complete data were obtained, and was positive in two nurses with a long history of smoking. The Salmonella/mammalian microsome assay detected eight of ten treatments in patients but failed to detect smokers. Four of nine patients receiving treatment were detected by the analysis of chromosomal aberrations.The SCE assay did not distinguish between the work and off‐work samples in either the exposed or control nurses. The exposed nurses, as a group, had slightly fewer SCEs than the controls due to the two smokers detected 'n the latter group. Chromosomal aberration was the only assay which showed significant difference between the two samples of the exposed nurses and, consequently, between the exposed and control nurses. These differences, however, arose primarily from a higher frequency of aberrations found among the exposed nurses in samples taken after a few days away from work, rather than at the end of their work period. There is no evidence that the increase was connected to occupational exposure.
Comparative studies on the genotoxic activity of mainstream smoke condensate from cigarettes which burn or only heat tobacco
Authors: Doolittle D. J. , Lee C. K. , Ivett J. L. , Mirsalis J. C. , Riccio E. , Rudd C. J. , Burger G. T. , Hayes A. W. 
Published: February 2007

AbstractThe in vitro genotoxic activity of mainstream cigarette smoke condensate (CSC) from cigarettes which heat but do not burn tobacco was compared to that of CSC from cigarettes which burn tobacco. CSCs from five cigarettes were compared. Three of the cigarettes [the Kentucky reference research cigarette (1R4F), a commercially available ultra‐low tar brand (ULT) and a commercially available ultra‐low tar menthol brand (ULT‐menthol)] burn tobacco while two of the cigarettes [a regular (TEST) and a menthol (TEST‐menthol)] heat tobacco. CSC from all cigarettes were collected by identical standard techniques, which involved collecting mainstream smoke particulate matter on Cambridge filter pads under FTC smoking conditions. The pads were extracted with DMSO, and the CSCs obtained [10 mg total particulate matter (TPM)/ ml DMSO] were evaluated at identical concentrations in an in vitro genetic toxicology test battery. CSCs from 1R4F, ULT, and ULT‐menthol cigarettes were mutagenic in Ames bacterial strains TA98, TA100, TA1537, and TA1538 in the presence of metabolic activation (S9 from Aroclor‐induced rat liver) but negative in strain TA1535. In the absence of metabolic activation, 1R4F, ULT, and ULT‐menthol CSCs were not mutagenic except for a weak response in strain TA1537 for the 1R4F and ULT CSCs. TEST and TEST‐menthol CSCs were nonmutagenic in all five bacterial strains, both with and without metabolic activation. CSCs from 1R4F, ULT, and ULT‐menthol cigarettes were positive in the CHO‐chromosomal aberration assay and in the CHO‐sister chromatid exchange assay both with and without metabolic activation while TEST and TEST‐menthol CSCs were negative in both assays, either with or without metabolic activation. CSCs from 1R4F, ULT, and ULT‐menthol cigarettes were weakly positive in inducing DNA repair in cultured rat hepatocytes while TEST and TEST‐menthol CSCs were negative in this assay. All five CSCs were nonmutagenic in the CHOHGPRT assay both with and without metabolic activation. CSCs from the 1R4F, ULT, and ULT‐menthol cigarettes were cytotoxic in the CHOHGPRT assay, both with and without metabolic activation, while TEST and TEST‐menthol CSCs were not cytotoxic under either condition. These results demonstrate that mainstream CSCs from the TEST and TEST‐menthol cigarettes are neither genotoxic nor cytotoxic under conditions where CSCs from 1R4F, ULT, and ULT‐menthol cigarettes are genotoxic and/or cytotoxic in a concentration‐dependent manner.
Antimutagens and anticarcinogens: A survey of putative interceptor molecules
Authors: Hartman Philip E. , Shankel Delbert M. 
Published: February 2007

AbstractIn this review recent publications are cited for a number of antimutagens. The molecules surveyed are potential or proven “desmutagens” or “interceptors.” These are biologically prevalent or synthetic molecules that are most often small metabolites proficient in binding to, or reacting with, mutagenic chemicals and free radicals. Many of this class of “blocking agents” are “soft” and “hard” nucleophiles with consequently varying abilities to react with particular classes of electrophiles, the major classes of direct‐acting mutagens. Although they serve as a first line of defense against mutagens and carcinogens, many interceptor molecules are under‐investigated with regard to their spectra of activity and their possible relevance to prophylaxis or treatment of human disease states.
Assay‐specific genotoxicity of N‐nitrosodibenzylamine to the rat liver in vivo
Authors: Schmezer P. , Pool B. L. , Lefevre P. A. , Callander R. D. , Ratpan F. , Tinwell H. , Ashby J. 
Published: February 2007

AbstractN‐Nitrosodibenzylamine (NDBzA) is mutagenic to Salmonella typhimurium and induces DNA strand breaks in isolated rat hepatocytes, yet it is reported to be non‐carcinogenic to the rat. Here we report that it is inactive in both the rat and mouse bone marrow micronucleus assays and in a rat liver autoradiographic assay for unscheduled DNA synthesis. It is, however, clearly active as a micronucleus‐inducing agent and mitogen in the rat liver and is capable of inducing single‐strand breaks in the DNA of rat liver. The origin and implications of this curious conflict of in vivo genotoxicity data are discussed. Irrespective of that discussion, it is concluded that NDBzA is genotoxic to the rat liver in vivo.
Spontaneous frequency of 6‐thioguanine resistant mutants in CHO‐AS52 cells after prolonged culturing in the absence of selective agents
Authors: Li Albert P. 
Published: February 2007

AbstractThe Escherichia coli xanthine‐guanine phosphoribosyl transferase (XPT) containing Chinese hamster ovary (CHO‐AS52) cells were studied in our laboratory to evaluate its general applicability in genotoxicity testing of industrial chemicals. Our initial effort was to evaluate the stability of the 6‐thioguanine sensitive phenotype. The CHO‐AS52 cells were cloned and cultured continuously for over 600 days in the absence of any selective agents. The spontaneous 6‐thioguanine resistant mutant frequency was quantified periodically. The frequency was found to increase continuously with time from approximately 20 × 10−6 to a plateau of approximately 250 × 10−6 in 122 days. The mutant frequency fluctuated around the plateau value up to the last day of our study, at 648 days after cloning. A similar observation was made for cells that were recloned or treated with aminopterin (to selectively kill 6‐TG resistant mutants) at approximately 450 days after the initial cloning. Our data suggest that the xpt gene was stably incorporated in the CHO cells.
The biochemical mechanisms of the plant activation of promutagenic aromatic amines
Authors: Wagner Elizabeth D. , Verdier Mary M. , Plewa Michael J. 
Published: February 2007

AbstractUsing specific monooxygenase and oxidase inhibitors in a plant cell/microbe coincubation assay, the biochemical mechanisms of the plant activation of two aromatic amines were compared. The biological endpoints included mutation induction, inhibition of mutagenicity, viability of the plant cells (activating system), and viability of the microbial cells (genetic indicator organism). The activation of m‐phenylenediamine by TX1 cells was mediated by enzyme systems that were inhibited by diethyldithiocarbamate, potassium cyanide, methimazole, ( + )‐catechin or acetaminophen. The inhibition by metyrapone was attended by toxicity in the plant cells. These data implicate a TX1 cell peroxidase and a FAD‐dependent monooxygenase in the plant activation of m‐phenylenediamine. The TX1 cell activation of 2‐aminofluorene was inhibited by diethyldithiocarbamate, 7,8‐benzoflavone, acetaminophen or ( + )‐catechin. An additional pathway of the plant cells in the activation of 2‐aminofluorene may involve a cytochrome P‐448‐type N‐hydroxylase.
Induction of mutagenesis and transformation in BALB/c‐3T3 clone A31‐1 cells by diverse chemical carcinogens
Authors: Lubet Ronald A. , Kouri Richard E. , Curren Roger A. , Putman Donald L. , Schechtman Leonard M. , McCormack J. R. 
Published: February 2007

AbstractBALB/c‐3T3 cells were employed to examine the genotoxic potential of a variety of known chemical carcinogens. BALB/c‐3T3 cells displayed a dose‐dependent transformation response to a variety of carcinogens (polycyclic hydrocarbons, methylating agents, ethylating agents, aflatoxin B1 [AFB1], and 4‐nitroquinoline‐N‐oxide [4‐NQO]). When the ability of these compounds to induce mutagenesis to resistance to the cardiac glycoside ouabain (OUAR) was examined, we found the short chain alkylating agents to be particularly effective mutagens, causing biologic effects at doses below those necessary to induce a transformation response. In contrast, the polycyclic hydrocarbons which were potent transforming agents were weaker, albeit significant, mutagens for the OUAR locus in this system, while AFB1 was quite weak. Further studies were performed with 5‐azacytidine (5‐AZA) and the nongenotoxic carcinogen cinnamyl anthranilate (CIN). 5‐AZA was a potent transforming agent, but failed to cause mutagenesis. CIN similarly caused in vitro transformation. When a series of eight structurally diverse compounds were examined in both the BALB/c‐3T3 and C3H10T1/2 mouse fibroblast transformation systems, the BALB/c‐3T3 system was shown to be sensitive to a wide variety of potential carcinogens, whereas the C3H10T1/2 system proved routinely sensitive only to the polycyclic hydrocarbons.
Study of mutational specificity in the lacl gene of escherichia coli as a window on the mechanisms of mutation
Authors: Glickman Barry W. , Elespuru R. K. 
Published: February 2007

AbstractWhereas in the past we had to be content with mutation induction and survival curves, the recently developed technologies permitting the rapid cloning and sequencing of mutant alleles have provided a new window through which to examine the nature of mutation. These technologies make it possible to determine the precise nature of the mutational alteration as well as the local DNA context. This information has contributed significantly to our knowledge of the mutational process including the identification of likely pre‐mutagenic lesions and the influence of DNA sequence and structure of the distribution of damage and its subsequent repair. This article discusses these issues as they relate to mutagenesis by alkylating agents.
Concentration‐response curves for ethylene‐oxide‐induced heritable translocations and dominant lethal mutations
Authors: Generoso W. M. , Cain K. T. , Cornett C. V. , Cacheiro N. L. A. , Hughes L. A. , Albertini R. J. , Casciano D. A. 
Published: February 2007

AbstractMale mice were subjected to repeated inhalation exposures to different concentrations (165, 204, 250, or 300 ppm) of ethylene oxide (EtO) during an 8.5‐week period. Transmitted clastogenic effects of these exposures were measured in terms of induction of dominant lethal mutations and heritable translocations. The concentration‐response curves for both endpoints are not linear but are markedly concave upward. Significant increases in dominant lethals were detected at all concentrations, except the lowest one. In comparison, the incidences of heritable translocations were significantly increased at all concentrations.