bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotoxic effects of fly ash in bacteria, mammalian cells and animals
Authors: Morris D. L. , Connor T. H. , Harper B. L. , Ward J. B. , Legator M. S. 
Published: February 2006

AbstractThe increasing use of fossil fuels has raised concerns about possible deleterious health effects of the final combustion product, fly ash. Seven ash samples from coal sources obtained from Battelle Columbus Laboratories were evaluated in the Salmonella/mammalian microsome mutagenicity assay to determine their mutagenic potential. While dimethyl sulfoxide extracts of five samples showed no mutagenicity, sample 102 caused an increase in the number of revertants per plate over controls in TA100 and TA98 with activation by liver homogenate (2‐fold and 2.4‐fold, respectively) and without (2‐fold and 6‐fold). This ash was thus evaluated in whole animal studies. Animals treated by inhalation or oral gavage were assayed for the presence of mutagens in the urine, micronuclei in polychromatic erythrocytes, and chromosomal aberrations in metaphase bone marrow cells. Those animals treated by inhalation were also examined for local damage in the lung. The assay for mutagens in the urine was negative as shown by the Ames assay with TA100 and TA98 and there was no increase in micronuclei or in metaphase aberrations. Histological sections from the animals treated by inhalation did not show the presence of particles, macrophage infiltrations and generalized lung damage. We tested the same fly ash with an in vitro cell transformation assay with the cell line Balb/c 3T3 subclone A31‐1‐13. Although there was not an increase in Type III foci, there was a dose‐dependent increase of Type II foci in the treated cells over the controls. In one assay, there was approximately a 14‐fold increase in Type II foci in the highest dose (2 mg/ml) compared to the solvent control. One other ash sample induced cell transformation without being markedly cytotoxic, while a third sample was highly toxic but did not induce transformation.
Tetrachloroethane, pentachloroethane, and hexachloroethane: Genetic and biochemical studies
Authors: Bronzetti G. , Morichetti E. , Carratore R. Del , Rosellini D. , Paolini M. , Cantelli‐Forti G. , Grilli S. , Vellosi R. 
Published: February 2006

AbstractTetrachloroethane (TTCE), pentachloroethane (PCE), and hexachloroethane (HCE) were tested in diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension test with and without mammalian metabolic activation (S9). TTCE, PCE, and HCE gave positive results on cells harvested from logarithmic growth phase; only PCE induced a significant increase (P ≤ .01) of mitotic gene conversion and point reverse mutation on cells from stationary growth phase with metabolic activation (S9).The in vivo effects on cytochrome P450 content (cyt. P450), pentoxyresorufin O‐dealkylase (P450‐like, class IIB, PROD), and ethoxy‐resorufin O‐deethylase (P448‐like, class IA, EROD) activities were examined in hepatic microsomes from mice 24 h after acute intoxication. All the halogenated hydrocarbons displayed a marked toxic effect as shown by the significant decrease in cyt. P450 levels (maximum of 76% decrease, with TTCE 753.2 mg/kg) and EROD (maximum of 69% decrease, with PCE 925.4 mg/kg), and to a lesser extent in PROD (maximum of 52.4% decrease, with HCE 3150 mg/kg). Although a general decrease of P450 functions was observed, the toxic effects of TTCE and PCE seem to be preferentially related to P448 forms.
Noncorrelative c‐myc and ras oncogene expression in squamous cell carcinoma cells with tumorigenic potential
Authors: Shuler Charles , Kurian Ponnamma , French Bernard T. , Noyes Inge , Sital Nirander , Hollering Jens , Trewyn Ronald W. , Schuller David , Milo George E. 
Published: February 2006

AbstractThe distribution of heterogeneous cell types within human tumors was examined, and the biological behavior of tumors and different tumor cell lines was evaluated following implantation into surrogate hosts. In situ hybridization and immunohistochemistry were used to examine the expression of oncogenes and localization of the squamous cell carcinoma cell surface‐associated antigens. Increased levels of H‐ras mRNA and p21 protein were present in six tumors, but enhanced c‐myc mRNA expression was observed in just two tumors. The distribution of oncogene mRNA and SCC antigen‐positive cells was not uniform throughout the tumor.Isolation of cells from the tumors was accomplished by cell culture, growth in soft agar, and growth in the nude mouse. One nontumorigenic immortalized cell line, SCC‐83‐01‐82, isolated by passage through soft agar, was treated with 50 μg/ml of methyl methane sulfonate (MMS). These MMS‐converted cells subsequently expressed a tumorigenic phenotype. In situ hybridization of the tumors that developed in nude mice revealed increased c‐myc and H‐ras mRNA expression. Serial passage of the MMS‐converted tumors in vivo was accompanied by consistent enhanced c‐myc expression. However, the levels of H‐ras and keratin mRNA expression decreased with passage in vitro. Northern blot analysis of c‐myc and H‐ras mRNA levels from the original SCC cell line showed no change in expression following MMS treatment. The data suggest that SCC‐83‐01‐82 is a premalignant cell line established from a mixed cell population in the tumor mass. It can be converted to a malignant phenotype by treatment with MMS, and the persistence of malignancy is under molecular control other than changes in the level of c‐myc and ras gene expression.
New structural concepts for predicting carcinogenicity in rodents: An artificial intelligence approach
Authors: Rosenkranz Herbert S. , Klopman Gilles 
Published: February 2006

AbstractThe Computer Automated Structure Evaluation (CASE) method for studying structure‐activity relationships has been applied to a data base of rodent carcinogens. It has been demonstrated that CASE is able to identify determinants embedded in the molecular structure which, with a high probability, predict rodent carcinogenicity. CASE has also identified determinants associated with the activity of non‐genotoxic carcinogens, thereby suggesting that there is a structural commonality in the activity of these molecules. The present study reveals that there are “universal” as well as species‐specific structural determinants of carcinogenicity. CASE was able to predict the carcinogenicity in rodents of certain endogenous pesticides in edible plants.
Tumor promotion: Models and assay systems
Authors: JamesFitzgerald D. , Yamasaki Hiroshi 
Published: February 2006

AbstractTumor promotion is defined operationally from two‐stage models of experimental carcinogenesis. It is, therefore, in a strict sense, possible to identify tumor promoters only from such models. The development and use of in vitro two‐stage cell transformation assays was a logical extension toward in vitro short‐term testing for tumor promoters. Another approach is to apply mechanistic knowledge of the tumor promotion process in developing end points for such assays. In this context, we have been examining the role of blocked gap‐junctional intercellular communication (GJIC) in tumor promotion, using in vitro and in vivo systems. Many promoters have been shown to block GJIC in vitro; our studies support the idea that inhibition of GJIC does play an important role in the promotion stage of BALB/c 3T3 cell transformation. In animal studies, we have shown that the rat liver tumor promoter phenobarbital can decrease the level of expression of the 32 Kd gap junction protein gene specifically in liver upon systemic exposure in rats. Further examination of the role of GJIC in tumor promotion is indeed warranted. Also, deployment of in vitro GJIC and transformation assay systems should provide useful short‐term tests for detecting tumor promoting activity of environmental chemicals.
Molecular analysis of reactive oxygen‐species‐induced mammalian gene mutation
Authors: Hsie Abraham W. , Xu Zhidong , Yu Yongjia , Sognier Marguerite A. , Hrelia Patrizia 
Published: February 2006

AbstractWe have studied the mutagenicity and toxicity of physical and chemical agents in the Chinese hamster ovary (CHO) cell line K1‐BH4 and its transformant, AS52. The AS52 cells lack the normal X‐linked mammalian hypoxanthine‐guanine phosphoribosyltransferase (hprt) gene but instead contain a single autosomally integrated copy of the bacterial equivalent, the xanthine‐guanine phosphoribosyltransferase (gpt) gene. We found that X‐rays and neutrons appear to be equitoxic to both cell types; however, these physical agents are approximately 10 times more mutagenic to the gpt gene of AS52 cells than to the hprt gene of K1‐BH4 cells. We reasoned that if reactive oxygens were to mediate the mutagenic effects of both radiomimetic chemicals and radiation, then reactive oxygen‐producing chemicals, such as streptonigrin and bleomycin, and oxidizing agents such as potassium superoxide and hydrogen peroxide, would exhibit similar levels of toxicity but different frequencies of mutants when assayed with the two cell lines. Our experiments fulfill such predictions. We postulate that the apparent hypermutability of AS52 cells probably results from a higher recovery of multi‐locus deletion mutants in AS52 cells than in K1‐BH4 cells, rather than a higher yield of induced mutants. Preliminary studies, using Southern blot and the polymerase chain reaction to analyze the mutational spectrum of the mutants, support our hypothesis that reactive oxygens induce deletion mutations in mammalian cells.
Biochemical epidemiology: Uses in the study of human carcinogenesis
Authors: Vineis Paolo , Faggiano Fabrizio , Terracini Benedetto 
Published: February 2006

AbstractThe use of biochemical markers may improve the potentialities of etiologic epidemiology. Exposure markers or markers of biologically effective dose allow better exposure assessment, therefore decreasing misclassification in epidemiological studies. Markers of individual susceptibility (such as metabolic polymorphism) permit the identification of subgroups of subjects at higher risk of cancer. In general, the integration of biochemical methods and an epidemiological design is helpful in the study of the sources of interindividual variability in response to carcinogenic stimuli. We review several investigations making use of biochemical measurements in the field of cigarette‐induced bladder cancer.
Micronuclei assay in cytokinesis‐blocked binucleated and conventional mononucleated methods in human peripheral lymphocytes
Authors: Channarayappa  , Nath J. , Ong T. 
Published: February 2006

AbstractStudies were performed to determine the genotoxic effect of cytochalasin‐B (CYB) and to compare the efficacy of the cytokinesis‐blocked binucleated cells (CB) for scoring micronuclei (MN) with the conventional mononuclear method, following treatment with mitomycin C and cyclophosphamide. The results show that 3–4 μg/ml of CYB induced maximum number of binucleated cells without any genotoxic effect and the frequency of MN in binucleated cells was higher than that in the mononucleated cells (P <0.05) but less than twofold. However, MN frequencies in binucleated cells were not equivalent to the frequencies of mononucleated cells, since MN in binucleated cells represent two nuclei. These results suggest that further study is required to consider CB method as a more reliable approach for scoring MN.
Induction of sister chromatid exchanges with hypotonic treatment
Authors: Kröger I. , Nowak C. 
Published: February 2006

AbstractHypotonic NaCl solutions and diluted culture medium were tested for induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (CA). Hypotonic treatment conditions were found to induce high frequencies of CA and SCEs. However, an increase in SCEs was observed only in cells that also had CA. Possible lesions and mechanisms leading to SCEs and CA are discussed.
Effects of quercetin, a plant flavonol, on the two‐stage transformation in vitro
Authors: Sakai A. , Sasaki K. , Mizusawa H. , Ishidate M. 
Published: February 2006

AbstractQuercetin was examined for the effects on the two‐stage chemical transformation of BALB/3T3 cells. Quercetin showed initiating action to induce transformation in the cells which were treated with quercetin and subsequently with 0.49 μM 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Both the proportion of dishes with transformed foci and the average number of foci per dish increased with the concentration of quercetin (15–45 μM). However, initiating treatment with quercetin did not induce transformation without subsequent TPA treatment. Quercetin inhibited the promotion caused by 0.49 μM TPA in the transformation initiated by 1.9 μM 3‐methylcholanthrene (MCA). The inhibitory effect of 30 μM quercetin was 56% in the number of foci per dish. Thus quercetin was found to have initiating effect on the transformation of BALB/3T3 cells, but to restrain the promotion by TPA.
32P‐assay of DNA adducts in white blood cells and placentas of pregnant women: Lack of residential wood combustion‐related adducts but presence of tissue‐specific endogenous adducts
Authors: Reddy M. Vijayaraj , Kenny Peter C. , Randerath Kurt 
Published: February 2006

AbstractResidential wood combustion (RWC), which has been increasingly used as a heating source, is of health concern because emissions from RWC contain carcinogenic polycyclic aromatic hydrocarbons (PAH). To assess health risk, the possible formation of PAH‐DNA adducts in white blood cells (WBC) and placentas of nonsmoking women exposed to RWC smoke during pregnancy was measured by a nuclease P1‐enhanced 32P‐postlabeling assay having a sensitivity limit of one lesion per 109–10 DNA nucleotides. DNA samples isolated from 12 exposed specimens (8 WBC, 4 placentas) and 13 unexposed control specimens (8 WBC, 5 placentas) were hydrolyzed to mononucleotides, which were then 32P‐labeled and separated by high‐resolution thin‐layer chromatography. Comparison of autoradiograms of exposed DNA samples with those of controls failed to show exposure‐related adducts. All placental DNA maps exhibited one major (47 ± 10%) and 12 minor extra spots, however, that were not seen on WBC‐DNA maps. These derivatives corresponded to an average of 12 (± 6) modifications in 109 nucleotides. Similarly, WBC DNA showed four spots that were absent in placental DNA and were not quantified because of their low levels. Neither placental nor WBC DNA adducts coincided chromatographically with the product formed by the reaction of benzo(a)pyrene diol epoxide I with N2 of guanine in DNA. Although these results suggest that RWC smoke does not elicit detectable levels of aromatic DNA adducts in humans, lack of evaluation of RWC exposure levels leaves some uncertainty in this conclusion. The results, however, clearly show that placental and WBC DNA contain covalent modifications that are unrelated to RWC exposure. These DNA derivatives may be caused by ingestion and/or inhalation of, or skin contact with, low levels of environmental genotoxicants or may arise from endogenous electrophiles of as yet unknown origin.
Metabolic activation in the fetal mouse salivary gland culture system with rat hepatocytes, rat S‐9, and human S‐9
Authors: Lyng R. Douglas , Scalf Robert , Monteith David 
Published: February 2006

AbstractThe usefulness of an in vitro assay for embryotoxicity may depend on the availability of metabolic activation systems that will function in the culture system. The fetal mouse salivary gland has been investigated as an in vitro assay system. To see if the glands would grow in the presence of metabolic activators and if the glands would react to metabolites known to be embryotoxic, the glands were grown in the presence of cyclophosphamide (CP) and several activation systems. These included isolated rat hepatocytes, uninduced rat S‐9, rat S‐9 induced with 3‐methylcholanthrene (3‐MC), rat S‐9 induced with Aroclor 1254, and human S‐9. Twenty salivary glands were isolated from 13 day embryos (plug day = 0) and were grown in each treatment for 48 h. One control had no activation system or CP, one had an activation system but no CP, and three treatments had the activation system and 25, 75, or 150 μg/ml CP. The S‐9 with cofactors and the appropriate amount of CP was contained in dialysis bags. The greatest suppression of salivary gland growth occurred in co‐culture with hepatocytes activating CP. The S‐9 induced by Aroclor 1254 was nearly as effective as the hepatocytes. The next most effective was a group with similar activity consisting of the uninduced rat S‐9 and the three samples of human S‐9. The 3‐MC‐induced S‐9 was the least effective in suppressing growth of salivary glands. All the activation systems tested can be used with the salivary gland culture system.
Teratogenicity of cobalt chloride in Xenopus laevis, assayed by the FETAX procedure
Authors: Plowman Marilyn C. , Peracha Hameed , Hopfer Sidney M. , Sunderman F. William 
Published: February 2006

AbstractThe teratogenicity of cobalt chloride (CoCl2) was tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure in the South African frog, Xenopus laevis. In five assays, beginning at 5 h post‐fertilization, groups of Xenopus embryos were incubated for 96 h in media that contained CoCl2 at concentrations ranging from 1.8 × 10−6 to 1.8 × 10−2 mol/L; control groups were incubated in the same medium without added CoCl2. At 101 h post‐fertilization, surviving embryos were counted, fixed in formalin, and examined by microscopy to score malformations and measure head‐to‐tail lengths. In control embryos, survival was ≥95% and malformations were ≥5%. Malformations were found in >99% of embryos exposed to Co2 + levels ≥56 μmol/L. Co2 +‐exposed embryos showed a concentration‐related pattern of malformations, comprising gut malrotation, ocular anomalies, kinked tail, craniofacial dysplasia, cardiac deformities, and dermal blisters. Other concentration‐dependent abnormalities, not categorized as malformations, included stunted growth, edema, ventral distention, and hypopigmentation. The median embryolethal concentration (LC50) of CoCl2 was 10.4 (SE ± 0.4) mmol/L; the median teratogenic concentration (EC50) was 25 (SE ± 2) μmol/L; the teratogenic index (Tl = LC50/EC50) was 416 (SE ± 13), indicating that CoCl2 is a potent teratogen for Xenopus laevis.
Statistical methods for analyzing developmental toxicity data
Authors: Piegorsch Walter W. , Haseman Joseph K. 
Published: February 2006

AbstractA description and review of methods for performing per‐litter analyses involving extrabinomial proportion response is provided. It is stressed that the litter should be regarded as the appropriate experimental unit for quantitative analysis in studies for teratogenic or heritable mutagenic effects. Attention is directed at statistical identification of possible treatment effects, such as a positive dose response to a chemical stimulus. The methods range from distribution‐free, nonparametric analyses to models involving parametric distributions such as the beta‐binomial density. It is seen that most current methods require computer implementation. When concern is raised over misspecification of assumptions critical to the statistical analysis, it is argued that relatively parameter‐free methods are appropriate for use. These include statistical bootstrapping and rank‐based analyses.
Genotoxicity of vanadium compounds in yeast and cultured mammalian cells
Authors: Galli A. , Vellosi R. , Fiorio R. , Croce C. Della , Carratore R. Del , Morichetti E. , Giromini L. , Rosellini D. , Bronzetti G. 
Published: February 2006

AbstractThe ability of vanadium compounds to induce genetic activity was investigated in D7 and D61M strains of Saccharomyces cerevisiae and in Chinese hamster V79 cell line.In our previous work, ammonium metavanadate (pentavalent form, V5) induced mitotic gene conversion and point reverse mutation in the D7 strain of yeast. The genotoxicity was reduced by the presence of S9 fraction, which probably reduced pentavalent vanadium to the tetravalent form.In the present study, vanadyl sulfate (tetravalent form, V4) induced no convertants and revertants in yeast cells harvested from stationary growth phase. With yeast cells from logarithmic growth phase, which contain high levels of cytochrome P‐450, a significant increase in genetic effects was observed. Further experiments, performed by treating cells harvested from logarithmic growth phase in the presence of cytochrome P‐450 inhibitors, indicated that the monooxygenase system influenced the genotoxicity of metavanadate while the genetic activity of vanadyl remained unaffected. Aneuploidy effect in the D61M strain of Saccharomyces cerevisiae was induced by either V5 or V4, confirming that vanadium compounds are potentially antitubuline agents in eukaryotic cells.Although these compounds are very toxic in V79 cells, no mutagenic effect was observed in the presence or in the absence of S9 fraction.
Relationship of cell death to cyclophosphamide‐induced ocular malformations
Authors: Peiffer Robert L. , McCullen Robert , Alles Ajit J. , Sulik Kathleen K. 
Published: February 2006

AbstractC57BL/6J mice were used to study the ocular teratogenic effects of cyclophosphamide administered to pregnant females on d 9 of pregnancy at a dose of 5 mg/kg body weight. Nile blue staining demonstrated increased cell death at the base of the optic stalk, in the optic vesicle, and in the perivesicular mesenchyme in treated embryos. Malformations studied at gestational d 11 and 16 by light and scanning electron microscopy included microphthalmos, microphakia, and aphakia and were predictable based upon patterns of increased cell death. These anomalies are similar to those reported with exposure to ethanol or isotretinoin on gestational d 7.
Comparative study of micronucleus assay and chromosomal aberration analysis in V79 cells exposed to ethylene oxide
Authors: Zhong Bao‐Zhen , Gu Zu‐Wei , Whong Wen‐Zong , Wallace William E. , Ong Tong‐Man 
Published: February 2006

AbstractMicronucleus formation and chromosomal aberration (CA) in V79 cells were compared for their sensitivity in response to ethylene oxide (EtO) treatment. The results indicate that EtO exposure for 30 min induced CAs in V79 cells at the concentration of 3,500 ppm or higher. A statistically significant difference (P<0.01) was found between treated and control groups at all concentrations tested based on percent aberrant cells. The increase was dose‐dependent with a correlation coefficient of 0.88. The aberrations found include chromatid and isochromatid breaks, fragments, minutes, and exchanges. Results of the micronucleus assay both in mononucleated and binucleated cells showed a slight but not statistically significant increase in micronuclei with doses between 457 to 4115 ppm. At the highest concentration tested (12344 ppm) EtO caused a significant increase in the micronucleus frequency (P<0.05). © 1992 Wiley‐Liss, Inc.
Influence of retinoids on sister chromatid exchanges and chromosomes in cultured human embryonic palatal mesenchymal cells
Authors: Watanabe Toshiaki , Pratt Robert M. 
Published: February 2006

AbstractThe cytogenetic effects of retinoids and their metabolites on human embryonic palatal mesenchymal (HEPM) cells were investigated in cell culture. Treatment with 13‐cis, 4‐oxo‐13‐cis‐, and all‐trans‐retinoic acids did not induce chromosomal structural aberrations even at high concentrations in the presence or absence of metabolic activation system. The frequencies of sister chromatid exchanges (SCE) tended to decrease in HEPM cells treated with retinoids in the absence of S‐9. 4‐Oxo‐13‐cis‐retinoic acid, which is one metabolite of 13‐cis‐retinoic acid, significantly decreased the SCE frequencies. The mitotic index decreased with increasing concentration of retinoic acids, indicating that retinoids inhibit cell proliferation in HEPM cells. We concluded that retinoids inhibit cell proliferation in HEPM cells in culture without causing DNA or chromosome damage. © 1992 Wiley‐Liss, Inc.