bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotoxic potency of three quinoline compounds evaluated in vivo in mouse marrow cells
Authors: McFee A. F. 
Published: February 2007

AbstractIn vitro assays of the genotoxicity of quinoline compounds have yielded varying indications of their potency, and only limited determinations have been reported following in vivo administrations. We have quantified chromosome aberrations (CA) and sister chromatid exchanges (SCE) in the marrow cells of mice that had been injected with quinoline, 8‐hydroxyquinoline, or 4‐nitroquinoline‐1‐oxide up to levels approaching lethal. Treatments with quinoline produced no consistent increase in the number of aberrations at either 17 or 36 hr after treatment and no significant increase in SCE numbers at either 23 or 42 hr. Similarly, 8‐hydroxyquinoline had no measurable effect on either CA or SCE but did tend to prolong the cell cycle. 4‐Nitroquinoline‐1‐oxide was a very potent inducer of both CA and SCE as well as an inhibitor of cell division.
Studies on the antimutagenic activities of garlic extract
Authors: Knasmüller Siegfried , de Martin Rainer , Domjan Gyula , Szakmary Akos 
Published: February 2007

AbstractExperiments with Salmonella tester strains indicated that aqueous garlic extract possesses anti‐mutagenic properties toward ionizing radiation, peroxides, adriamycin, and N‐methyl‐N′‐nitronitrosoguanidine. The assumption that radical scavenging garlic constituents, i.e., molecules with sulfur moieties, might be responsible for the inhibitory effect of aqueous extract toward mu‐tagenesis induced by radiation and radiomimetic compounds was confirmed by the results of subsequent experiments; 1) garlic extract attenuated the lethal effects of y‐rays on repair deficient E. coli strains; 2) the garlic constituent allicin (thio‐2‐propene‐1 ‐sulfinic acid S‐allyl ester) is partly responsible for the reduced radiation‐induced mutagenesis in Salmonella typhi‐murium TA 102. No such inhibitory effects were detected with alliin (S‐allyl‐L‐cysteine sulfoxide) or cysteine; 3) aqueous garlic extract inhibited hydrogen‐peroxide‐induced lipid peroxidation. Results obtained in preliminary experiments with Chinese hamster ovary cells suggest that the antimutagenic properties of garlic extract are not restricted to procaryotic cells.
Comparative yields of mutagens from cigarette smokers' urine obtained by using solid‐phase extraction techniques
Authors: Williams R. W. , Pasley T. , Watts R. , Inmon J. , Fitzgerald J. , Claxton L. 
Published: February 2007

AbstractUrine from cigarette smokers was prepared for mutagenicity testing by extracting mutagens with solid‐phase extraction columns. Commercially available prepacked bonded silicas (octadecyl, cyclohexyl, cyanopropyl) were compared for their ability to concentrate the urinary mutagens. Recovered urinary metabolites were evaluated for mutagenic activity by using a microreversion assay with Salmonella typhimurium. Dose‐response data indicated that while mutagens were recovered by all three adsorbents, samples prepared by using the bonded cyanopropyl columns yielded the most bioactivity and/or the least amount of test organism toxicity. Varying pH of the urine was found to influence only the basified samples in terms of mutagenic recovery with the cyanopropyl base. Combinations of different adsorbents were not found to offer significant advantages over use of a singular extraction adsorbent.
Superoxide generation by photomediated redox cycling of anthraquinones
Authors: Hartman Philip E. , Goldstein Marc A. 
Published: February 2007

AbstractAnthraquinones (AQs) comprise one important class of secondary metabolites predominantly produced by fungi and higher plants but also produced by a variety of other organisms. Humans orally ingest AQs from environmental sources as well as through direct use as nonpre‐scription laxatives, and some AQ derivatives are used as topically applied antipsoritic agents. Some AQs are mutagenic. We present evidence that aqueous solutions of several AQs in the presence of an appropriate reducing agent and dissolved oxygen generate superoxide when they are illuminated with broad‐spectrum light. Redox cycling of AQs could be responsible for some aspects of their toxicity in biological systems.
Long‐term effects of triethylenemelamine exposure on mouse testis cells and sperm chromatin structure assayed by flow cytometry
Authors: Evenson D. P. , Baer R. K. , Jost L. K. 
Published: February 2007

AbstractThe toxic and potentially mutagenic actions of triethylenemelamine (TEM) on mouse body and testis weights, testicular cell kinetics, sperm production, sperm head morphology, and sperm chromatin structure were assessed in two experiments. The first experiment examined effects of four dose levels of TEM, assayed 1, 4, and 10 wk after toxic exposure. In the second study, effects from five dosage levels were measured at 1, 4, and 10 wk, and the highest dosage level was evaluated over 44 wk.TEM produced an expected dose related loss of spermatogenic activity and subsequent recovery as determined by dual‐parameter (DMA, RNA) flow cytometry (FCM) measurements of testicular cells. Both testicular weights and caudal sperm reserves remained generally below controls after 44 wk recovery following exposure to the highest (1.0 mg/kg daily x 5) dosage. Chromatin structure alterations, defined as increased susceptibility to DNA denaturation in situ, and sperm head morphology were highly correlated (.87‐.93, P>.001) with dose and with each other. Data obtained from the sperm chromatin structure essay (SCSA) on fresh sperm was highly correlated with measurements of aliquots of the same sample collected over 44 wk, frozen, and then measured on the same day. Sperm head morphology and sperm chromatin structure remained abnormal at 44 wk for the 1.0 mg/kg TEM dosage, suggesting that the abnormalities, present long after the initial toxic response, may be a result of mutation. This study demonstrates that flow cytometry provides a unique, rapid, and efficient means to measure effects of reproductive toxins and potential mutagens.
Chromosomal aberrations and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. IV. Results with 15 chemicals
Authors: Ivett J. L. , Brown B. M. , Rodgers C. , Anderson B. E. , Resnick M. A. , Zeiger E. 
Published: February 2007

AbstractThe National Toxicology Program has undertaken a study to assess the ability of four genetic toxicology assays to predict the carcinogenicity of chemicals in 2‐year rodent studies [Tennant et al.: Science 236:933–941, 1987]. Two of the assays, used for evaluating in vitro cytogenetic damage, were the SCE and chromosome aberration assays in Chinese hamster ovary cells. The results and data for 15 of the chemicals tested in these two assays are presented here. Each chemical was tested with and without exogenous metabolic activation. The chemicals tested were bisphenol A, 2‐chloroethanol, C.I. acid orange 10, C.I. disperse yellow 3, C.I. solvent yellow 14, cytembena, D&C red 9, 1,2‐dibromoethane, FD&C yellow 6, malaoxon, D, L‐menthol, phenol, sulfisoxazole, titanium dioxide, and tris(2‐ethylhexyl)phosphate. In vitro cytogenetic results from the other chemicals presented by Tennant et al. (Science 236:933–941, 1987) have been published by Galloway et al. (Environmental and Molecular Mutagenesis 10(Suppl 10):1–175, 1987 ), Gulati et al. (Environmental and Molecular Mutagenesis 13:133–193, 1989), and Loveday et al. (Environmental Mutagenesis 13:60–94).
Assessment of the genotoxicity of calcium cyclamate and cyclohexylamine
Authors: Brusick David , Cifone Maria , Young Robert , Benson Sky 
Published: February 2007

AbstractCalcium cyclamate and its major metabolite cyclohexylamine have been subjected to numerous evaluations for genetic activity. With the exception of studies for chromosome damage, the results have been negative. Results from a wide range of in vitro and in vivo cytogenetic assays ranged from clearly negative to various degrees of clastogenicity. Interpretation of the cytogenetic studies has been complicated by the conflicting responses, although some of the positive effects seem to be the consequence of secondary effects produced by high ion levels and excessive toxicity.In the studies presented here calcium cyclamate and cyclohexylamine were tested for mutagenic activity using an in vitro mammalian cells assay for gene mutation and an in vitro unscheduled DNA synthesis assay in rat hepatocytes with the Drosophila sex‐linked recessive lethal assay. Calcium cyclamate was not genetically active in any of the three assays when tested to the maximum possible concentrations. The compound was largely nontoxic but did show some evidence of cytotoxicity in rat hepatocytes at concentrations of 1 mg/ml and higher. Cyclohexylamine was also negative in the three assays, but was considerably more cytotoxic at the concentrations used.The results from the three studies conducted in this evaluation are in general agreement with the majority of published genetic toxicology data for these two chemicals and indicated that the calcium cyclamate and cyclohexylamine have no direct, intrinsic genotoxicity of the type measured by these assays.
Quinoline: Unscheduled DNA synthesis and mitogenesis data from the rat liver in vivo
Authors: Ashby J. , Mohammed R. , Lefevre P. A. , Bandara L. 
Published: February 2007

AbstractQuinoline is a specific and potent carcinogen to the rat and mouse liver. Studies are described here in which it was evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the rat liver in vivo. Although some individual animals showed indications of a marginal response, the absence of clear group positive responses and the lack of an obvious dose relationship precluded the classification of quinoline as positive. The analogous NTP non‐carcinogen 8‐hydroxy‐quinoline was shown also to be devoid of UDS activity. Quinoline did, however, induce a potent mitogenic response in the rat liver between 24 and 48 hr after oral dosing of 200–500 mg/kg. Under similar conditions of test, 8‐hydroxyquinoline was essentially inactive. These data represent a further instance in which mitogenicity in the liver appears to correlate better with carcinogenicity than does genotoxicity; but it may not be that simple, as discussed in the text. A single dose of quinoline was shown to act as a replacement for surgical partial hepatectomy in the liver micronucleus assay described by Tates, consistent with its potent mitogenicity.
Evidence for an involvement of thymidine kinase in the excision repair of ultraviolet‐irradiated herpes simplex virus in human cells
Authors: Intine Robert V. A. , Rainbow Andrew J. 
Published: February 2007

AbstractA wild‐type strain of herpes simplex virus type 1 (HSV‐1:KOS) encoding a functional thymidine kinase (tk+) and a tk‐ mutant strain (HSV‐1:PTK3B) were used to study the role of the viral tk in the repair of UV‐irradiated HSV‐1 in human cells. UV survival of HSV‐1:PTK3B was substantially reduced compared with that of HSV‐1:KOS when infecting normal human cells. In contrast, the UV survival of HSV‐1:PTK3B was similar to that of HSV‐1:KOS when infecting excision repair‐deficient cells from a xeroderma pigmentosum patient from complementation group A. These results suggest that the repair of UV‐irradiated HSV‐1 in human cells depends, in part at least, on expression of the viral tk and that the repair process influenced by tk activity is excision repair or a process dependent on excision repair.
Employment of adult mammalian primary cells in toxicology: In vivo and in vitro genotoxic effects of environmentally significant N‐nitrosodialkylamines in cells of the liver, lung, and kidney
Authors: Pool Beatrice L. , Brendler S. Y. , Liegibel U. M. , Tompa A. , Schmezer P. 
Published: February 2007

AbstractThis report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single‐strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N‐nitrosamines with unique organ‐specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell‐specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.
Sodium fluoride is a less efficient human cell mutagen at low concentrations
Authors: Crespi Charles L. , Seixas Gerald M. , Turner Thomas , Penman Bruce W. 
Published: February 2007

AbstractSodium fluoride was found to induce gene‐locus mutations at the thymidine kinase (tk) and hypoxanthine guanine phosphoribosyl transferase (hgprt) loci in human lymphoblastoid cells. A single, 28 hr exposure to up to 600 μg/ml sodium fluoride induced a concentrationdependent increase in mutant fraction at both gene loci and reduced cell survival to 12% relative to negative control cultures. When cells were exposed to sodium fluoride concentrations that were only minimally toxic using a 20 day treatment protocol, no detectable induction of mutation was ob‐served at the the hgprt locus, and induction of mutation was observed at the tk locus only for treatment with 65 μg/ml sodium fluoride; exposure to 50 and 35 μg/ml sodium fluoride did not induce detectable mutation. The assay protocol used was of sufficient statistical sensitivity to detect the level of mutation predicted based on a linear extrapolation of data obtained from a 28 hour exposure. The implications of these observations with regard to the extrapolability of mutagenicity data to low concentrations are discussed.
Mutational specificity of alkylating agents and the influence of DNA repair
Authors: Horsfall Michael J. , Gordon Alasdair J. E. , Burns Philip A. , Zielenska Maria , van der Vliet Gabrielle M. E. , Glickman Barry W. 
Published: February 2007

AbstractAlkylating treatments predominantly induce G: C = > A: T transitions, consistent with the predicted significance of the miscoding potential of the O6‐alG lesion. However, the frequency and distribution of these events induced by any one compound may be diagnostic. SN1 agents that act via an alkyldiazonium cation, such as the N‐nitroso compounds, preferentially generate G:C = > A : T transitions at 5′‐RG‐3′ sites, while the more SN2 alkylsulfates and alkylalkane‐sulfonates do not. The precise nature of this site bias and the possibility of strand bias are target dependent. The extent of this site bias and the contribution of other base substitutions are substituent size dependent. A similar 5′‐RT‐3′ effect is seen for A:T = > G:C transitions, presumably directed by O4‐alT lesions. The 5′‐RG‐3′ effect, at least, likely reflects a deposition specificity arising from some aspect of helix geometry, although it may be further exaggerated by alkylation‐specific repair. Excision repair appears to preferentially reduce the occurrence of ethylation‐induced G:C = > A:T and A:T = > G:C transitions at sites flanked by A:T base pairs. This may be due to an enhancement of the helical distortion imposed by damage at such positions. A similar effect is not seen for methylation‐induced mutations and in the case of propyl adducts, the influence of excision repair on the ultimate distribution of mutation cannot be as easily defined with respect to neighbouring sequence.
Maternal effect on micronucleus induction in MS/Ae mice
Authors: Sutou Shizuyo , Sato Seiji 
Published: February 2007

AbstractMS/Ae mice, which are mutagen‐sensitive in both the dominant lethal test and micronucleus test, and CD‐1 mice, which are the parental strain of MS/Ae, were mated in all four possible combinations. Both male and female offspring were subjected to the micronucleus test using mitomycin C (MMC), colchicine (Col), and 6‐mercaptopurine (6‐MP). Col showed equivocal results. However, MMC and 6‐MP showed differential responses in that both male and female offspring from CD‐1 dams had lower incidences of micronucleated polychromatic erythrocytes than those from MS/Ae dams regardless of sire strain. In addition, body weights of offspring from MS/Ae dams were lower than those from CD‐1 dams regardless of sire strain. Numbers of offspring from MS/Ae dams tended to be smaller than those from CD dams. These results suggest that the traits of MS/Ae mice are associated more with maternal factors than with paternal ones.
Evaluation of genotoxic effects of the herbicide dicamba using in vivo and in vitro test systems
Authors: Perocco P. , Ancora G. , Rani P. , Valenti A. M. , Mazzullo M. , Colacci A. , Grilli S. 
Published: February 2007

AbstractThe genotoxic effects of the herbicide dicamba have been studied by measuring 1) the unwinding rate of liver DNA from intraperitoneally (i.p.) treated rats (fluorimetric assay); 2) DNA repair as unscheduled DNA synthesis (UDS) induced in cultured human peripheral blood lymphocytes (HPBL); and 3) sister chromatid exchanges (SCE) in HPBL. Results show that dicamba is capable of inducing DNA damage since it significantly increases the unwinding rate of rat liver DNA in vivo and also induces UDS in HPBL in vitro in the presence of exogenous metabolic activation (S‐9 mix). Furthermore, dicamba causes a very slight increase in SCE frequency in HPBL in vitro.
Transgenic chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis
Authors: Klein Catherine B. , Rossman Toby G. , Skopek T. R. 
Published: February 2007

AbstractThe Escherichia coli gpt gene coding for xanthine‐guanine phosphoribosyl transferase has been stably transfected into HPRT− Chinese hamster V79 cells. Several gpt− cell lines have been established, which retain the sequence(s) even after long‐term culture without selection for gpt. Each cell line exhibits a characteristic spontaneous mutation frequency (10−5 to 10−2 in 6‐thioguanine (6TG) selection. While spontaneous mutagenesis to gpt− occurs rather frequently for most cell lines, it cannot be correlated with either the number of plasmid integration sites or deletion of the plasmid sequence(s). One transgenic cell line (g12), which continuously maintains a low spontaneous mutation frequency (˜3 × 10−5), was used in comparative mutagenesis studies with wild‐type V79 cells (gpt vs. hprt).Aklylating agents such as N‐methyl‐N×‐nitro‐N‐nitrosoguanidine (MNNG) and β‐propiolactone (BPL) are shown to be equally toxic and mutagenic in both g12 and V79 cells. UV and X‐rays are also equally toxic to both cell lines. The gpt locus of the g12 transfectants, however, is two to three times more sensitive to UV and 2.5—4.5 times more sensitive to X‐ray mutagenesis than the endogenous hprt of wild‐type V79 cells. The data presented here suggests that g12 cells may be useful to study mammalian mutagenesis by agents which yield limited response at the hprt locus. Future studies with these transgenic cells and other transgenic lines are planned to compare the mutability and repair of the same gene (gpt) at different integration sites in mammalian cells.
Melanin photosensitizes ultraviolet light (uvc) dna damage in pigmented cells
Authors: Huselton Christine A. , Hill Helene Z. , O'Neill J. P. 
Published: February 2007

AbstractMelanins, pigments of photoprotection and camouflage, are very photoreactive and can both absorb and emit active oxygen species. Nevertheless, black skinned individuals rarely develop skin cancer and melanin is assumed to act as a solar screen. Since DNA is the target for solar carcinogenesis, the effect of melanin on Ultraviolet (UV)‐induced thymine lesions was examined in mouse melanoma and carcinoma cells that varied in melanin content. Cells prelabeled with 14C‐dThd were irradiated with UVC; DNA was isolated, purified, degraded to bases by acid hydrolysis and analyzed by HPLC. Thymine dimers were detected in oil of the extracts of irradiated cells. Melanotic and hypomelanotic but not mammary carcinoma cell DNA from irradiated cells contained hydrophilic thymine derivatives. The quantity of these damaged bases was a function of both the UVC dose and the cellular melanin content. One such derivative was identified by gas chromatography—mass spectroscopy as thymine glycol. The other appears to be derived from thymine glycol by further oxidation during acid hydrolysis of the DNA. The finding of oxidative DNA damage in melanin‐containing cells suggests that melanin may be implicated in the etiology of Caucasian skin cancer, particularly melanoma. Furthermore, the projected decrease in stratospheric ozone could impact in an unanticipated deleterious manner on dark‐skinned individuals.
Acetaldehyde‐induced mutation at the hprt Locus in Human Lymphocytes In Vitro
Authors: He Sai‐Mei , Lambert Bo , McCormick J. J. 
Published: February 2007

AbstractAcetaldehyde (Aa) induces chromosomal aberration and sister chromatid exchange in a variety of test systems, but has not previously been evaluated for its ability to induce gene mutation in mammalian cells. We have studied the mutagenic effect of Aa at the hypoxanthine‐guanine phosphoribosyl transferase (hprt) locus in human lymphocytes in vitro by using the T‐cell cloning technique and selection of mutant cell clones in medium containing thioguanine. Cells treated with 1.2 — 2.4 mM Aa for 24 hr or 0.2 — 0.6 mM Aa for 48 hr showed a dose‐dependent decrease of cell survival and a 3‐ to 16‐fold increase of the mutant frequency. The inverse relationship between cell survival and mutant frequency was linear down to a relative survival of 15%, and showed a similar slope in the 24‐hr and 48‐hr treatment experiments. Forty‐one mutant T‐cell clones derived from cultures treated with 1.2 or 2.4 mM Aa and 15 from untreated controls were expanded for DNA extraction and Southern blot analysis to study deletion mutation using a full length hprt cDNA probe, and clonal identity on the basis of T‐cell receptor rearrangements. In the culture with a 16‐fold increase of mutant frequency, 4 out of 10 independent mutants (40%) showed partial deletions extending beyond the 3′ coding sequences of the hprt gene. Two of 22 independent mutants derived from the other treated cultures with at most a 6‐fold increase of mutant frequency, and 1 of 11 independent control clones showed rearrangement of the hprt gene, none of which affected the 3′‐end of the hprt gene. These results show that Aa is capable of inducing gene mutation at the hprt locus in human cells, and suggest that deletion mutation affecting the 3′‐end of the gene may be a major type of Aa‐induced mutation of this locus.
Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low‐dose exposure: Ethylene oxide as an example
Authors: Rhomberg Lorenz , Dellarco Vicki L. , Siegel‐Scott Cheryl , Dearfield Kerry L. , Jacobson‐Kram David , Malling H. V. 
Published: February 2007

AbstractThis paper explores how quantitative risk assessment methods might be extended to analysis of risks to the human germ line. High inhalation exposures to ethylene oxide are reported to cause heritable translocations in male mice with a steep and nonlinear dose‐response curve. We explore quantitative estimation of risk to humans from low exposures based on these animal data, addressing questions of tissue dosimetry for this alkylating agent, expected equivalency of doses across species, germ‐cell sensitivity, and extrapolation of dose‐response relationship to low exposure levels. Various dose‐response models are discussed in terms of their applicability to genetic end points and their ability to reflect the underlying basis of induced heritable translocations.