bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenesis, micronuclei, and carcinogenesis in the rat liver: Some basic inconsistencies
Authors: Ashby J. , Lefevre P. A. 
Published: February 2007

AbstractThe rodent liver carcinogen, mitogen, and per‐oxisome proliferator, methylclofenapate (MCP), has been investigated as a chemical mitogen for use in the rat liver micronucleus assay. A series of experiments comparing MCP with the potent mitogen 4‐acetylaminofluorene (4AAF) and with 2/3 partial hepatectomy showed unexpected differences between the three treatment regimes as monitored by the expression of micronucleated hepatocytes (MH) in livers initiated with N‐nitrosodimethylamine (NDMA). These differences were observed in both the profile of MH induction, as a function of time after mitogenic stimulation, and in the magnitude of response. There was no correlation between the magnitude of MH induction and the degree of mitoigenesis triggering the MH induction. It is concluded that the yield of MH observed in a rat liver micronucleus assay is not a simple function of the level of DNA damage induced by the initiating agent (here NDMA). This indicates the need for caution in the interpretation of data obtained in the liver micronucleus assay for chemicals of unknown carcinogenicity. The use of acridine orange as a fluorescent stain for use with isolatd hepatocytes is described. © 1992 Wiley‐Liss, Inc.
Adaptive response of vibrio cholerae and escherichia coli to nitrofurantoin
Authors: Basak Jayasri , Mukherjee U. , Chatterjee S. N. 
Published: February 2007

AbstractPretreatment with sublethal doses of nitrofurantoin induced adaptive response in both Vibrio cholerae and Escherichia coli cells as indicated by their greater resistance to the subsequent challenging doses of the same drug. Adaptive response was maximum corresponding to pretreatment drug concentrations of 0.40 μg/ml and 0.015 μg/ml respectively for V. cholerae OGAWA 154 (wild type) and E. coli K‐12 AB 2463 (recA−) cells. Adaptive response was inhibited by chloramphenicol (100 μg/ml) indicating the need of concomitant protein synthesis. Induction of adaptive response in recA deficient E. coli cells indicated that it was different from the conventional “SOS” response. Melting temperature of DNA of V. cholerae cells subjected to adaptive (0.4 μg/ml for 1 hr) and challenging (120 μg/ml for 1 hr) doses of nitrofurantoin (76°C) was closer to that of native DNA (75°C) vis‐a‐vis DNA isolated from nonadapted and drug treated cells (77.5°C). Also, DNA isolated from V. cholerae cells subjected to adaptive and challenging doses of the drug revealed the presence of fewer interstrand cross‐links (16% reversible DNA) vis‐a‐vis DNA from nonadapted but drug treated cells (55% reversible DNA). Photomicrographic studies revealed that V. cholerae cells that were nonadapted but drug treated grew into long filamentous forms (4.25 ± 2.97 μm) whereas those subjected to both adaptive and challenge doses of the drug exhibited much less filamentation (2.08 D̀ 0.84 μm) vis‐a‐vis native cells (1.42 ± 0.5 μm). Similar results on DNA melting temperature, cross‐links in DNA, and filamentation of cells were obtained for E. coli AB 2463 (recA−) cells subjected to adaptive and challenging treatments with nitrofurantoin. Almost equal degree of resistance against nitrofurantoin could be induced in both V. cholerae OGAWA 154 (wild type) and E. coli strain PJ3 (AB 1157 ada−) when these cells were pretreated with nontoxic doses of hydrogen peroxide or nitrofurantoin. Evidence obtained in this work on the nature of the nitrofurantoin induced adaptive response with particular references to the oxidative and/or alkylating DNA damages were discussed. Nitrofurantoin induced adaptive response appeared similar to that elicited by furazolidone in V. cholerae cells and appeared to be directed towards oxidative and not alkylating adaptive repair pathway. © 1992 Wiley‐Liss, Inc.
Comparison of acyltransferase‐mediated mutagenicity and nucleic acid binding of n‐acetoxy‐4‐acetylaminobiphenyl by hepatic and bladder microsomes from rats and dogs
Authors: Swaminathan Santhanam , Hatcher James F. 
Published: February 2007

AbstractAcyltransferase‐mediated mutagenic and metabolic activation of N‐acetoxy‐4‐acetylaminobiphenyl (N‐OAc‐AABP) by hepatic tissues of rats and dogs were compared. N‐OAc‐AABP was mutagenic in Salmonella typhimurium TA98 even in the absence of exogenous enzyme(s). However, supplementation with hepatic microsomes from dogs showed a dose‐dependent increase in mutagenicity of N‐OAc‐AABP, whereas under the same conditions, rat microsomes were inactive. Incubation of liver microsomes with RNA showed that 46.4 and 11.2 nmole of [3H]N‐OAc‐AABP were bound/mg RNA/mg protein with dogs and rats, respectively. The hepatic microsome‐mediated binding and mutagenicities of N‐OAc‐AABP were blocked by paraoxon, suggesting the involvement of deacetylase(s) in the activation process. Analyses of the in vitro incubates of N‐OAc‐AABP with rat and dog liver microsomes revealed the O‐deacetylation product N‐hydroxy‐4‐acetylaminobiphenyl (N‐OH‐AABP) as the major metabolite. The ratios of O‐deacetylation of N‐O[14C]Ac‐AABP versus N‐deacetylation of N‐OAc‐[14C]AABP for hepatic microsomes from dogs and rats were 2.9 and 7.2, respectively. The O‐ and N‐deacetylases are also distributed in bladder tissues and their activities in comparison to the hepatic tissues were lower and amounted to 14.2 and 5.0 nmoles (O/N‐deacetylation ratio 2.8) for dogs and 14.8 and 1.7 nmoles per mg protein per min (O/N‐ratio of 8.7) for rats. The microsomes from bladder tissues also catalyzed the binding of [3H]N‐OAc‐AABP to RNA and enhanced its mutagenic response in TA98, both of which were blocked by paraoxon. The occurrence of deacetylase(s) in the target tissues of the bladder carcinogen 4‐acetylaminobiphenyl (AABP) suggests that metabolic activation of some of the proximate metabolites could occur within these target organs. Furthermore, since the O‐deacetylation product N‐OH‐AABP is relatively innocuous compared to the N‐deacetylation product N‐acetoxy‐4‐aminobiphenyl, these results imply that the refractiveness of rats for 4‐aminobiphenyl or AABP‐induced bladder carcinogenesis might in part be associated with the higher ratios of microsomal O/N‐deacetylase activities. Thus susceptibility to arylamine or arylacetamide‐induced liver and bladder carcinogenesis might be influenced by the microsomal deacetylases. © 1992 Wiley‐Liss, Inc.
Decemtione (imidan)‐induced single‐strand breaks to human dna, mutations at the hgprt locus of v79 cells, and morphological transformations of embryo cells
Authors: Slameňová D. , Dušinská M. , Gábelová A. , Bohušová T. , Ruppová K. 
Published: February 2007

AbstractTo study the genotoxic activity of Decemtione (Imidan), this substance was subjected to a series of tests. After preliminary cytotoxicity testing, the capacity of Decemtione to damage human DNA was determined by alkaline elution of DNA and DNA unwinding. Both tests gave positive results, suggesting that Decemtione was able to induce single‐strand breaks in DNA. This capacity was higher in the absence and lower in the presence of the S9 fraction. The potential mutagenicity of Decemtione was followed on the basis of its ability to induce resistance to 6‐thioguanine in V79 hamster cells. Unlike the induction of single‐strand breaks, Decemtione showed, in the absence of the metabolic activation system, a very weak mutagenic effect, which was, however, significantly higher in the presence of the S9 fraction. The ability of the substance to transform diploid cells under in vitro conditions was followed on the basis of morphological transformation of Syrian hamster embryo cells. The results showed that Decemtione, like positive carcinogenes, induced a significant elevation in morphologically transformed colonies of embryo cells. The results suggest a carcinogenic potential of this organo‐phosphate insecticide. © 1992 Wiley‐Liss, Inc.
Comparison of rat liver parenchymal and nonparenchymal cells in the activation of promutagens
Authors: Teepe Annette G. , Beck Dale J. , Li Albert P. 
Published: February 2007

AbstractWhile the liver consists of both parenchymal cells (PC) and nonparenchymal cells (NPC), virtually all studies on promutagen activation have been performed using PC. To evaluate the comparative roles of PC and NPC in promutagen activation, we cocultivated a cell line generally considered to have an insignificant level of xenobiotic metabolism, Chinese hamster ovary (CHO) cells, with either PC, NPC, or a combination of both. The mixed culture was treated with two promutagens: dimethylnitrosamine (DMN) and 3‐methylcholanthrene (3‐MC). The induction of 6‐thioguanine resistant mutants was evaluated using the well‐established CHO/hypoxanthine‐guanine phosphoribosyl transferase (HGPRT) assay. Activation of promutagens, as indicated by an increase in mutant frequency in CHO cells, was observed only when the PC were present with the CHO cells during the treatment period. No activation was observed with NPC. Coculturing of PC and NPC yielded essentially the same results as PC alone. P‐450 mixed function monooxygenase activity measured by the 7‐ethoxycoumarin‐O‐deethylase assay further substantiates that PC had a significantly higher xenobiotic metabolism activity than NPC. Our study therefore indicates that PC, not NPC, are the major cell population in the liver responsible for the activation of promutagens. © 1992 Wiley‐Liss, Inc.
The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane
Authors: Dillon Deborah , Edwards Ian , Combes Robert , McConville Malcolm , Zeiger Errol 
Published: February 2007

AbstractDichloromethane (DCM) vapour by inhalation is carcinogenic to rodents and is an in vivo rodent cell clastogen and a bacterial mutagen. It has been suggested that the bacterial mutagenicity of DCM is mediated by glutathione (GSH) conjugation. The involvement of endogenous and exogenous GSH in the conversion of DCM to a bacterial mutagen has been studied in a vapour phase protocol using wild‐type and GSH‐deficient (NG54; gsh) Salmonella typhimurium TA100 strains in the presence and absence of various rat liver fractions. The effect of the duration of exposure was also investigated in these Salmonella strains and in E. coli WP2 uvrA pKM101. Dose‐ and time‐related increases in revertants occurred with all metabolic activation systems used (without exogenous metabolic activation; with Aroclor‐induced rat liver S9, microsomes, or cytosol fractions), with minor quantitative differences among the 3 strains. Mutagenicity was marginally highest in the presence of cytosol at the highest DCM concentrations. Strain NG54 gsh, which contains approximately 25% of the TA100 level of GSH/μg protein, was slightly less responsive to DCM‐induced mutagenicity than TA100. Addition of 0.33 μmoles/plate of GSH had little effect on the mutagenic responses of TA100 or NG54 in the presence or absence of S9. In these 2 strains, exogenous S9 produced small increases in mutagenicity at the highest concentrations of DCM (2 and 4% v/v). These results suggest that if an interaction between DCM and GSH is required for the activation of DCM to a bacterial mutagen, it occurs at low levels of endogenous GSH and is not significantly affected by GSH supplementation. © 1992 Wiley‐Liss, Inc.
Elevation of sister chromatid exchange frequency in transformed human fibroblasts following exposure to widely used aminoglycosides
Authors: McDaniel Lisa D. , Schultz Roger A. 
Published: February 2007

AbstractAminoglycosides are a class of antibiotics that interfere with protein translation. Geneticin and hygromycin are two such agents, which have been shown to exhibit highly toxic effects in mammalian cells. Cloned bacterial genes, which inactivate these antibiotics, have facilitated the establishment of dominant selection systems, which are widely used in eukaryotic molecular genetics. We have examined the effect of aminoglycosides on the sister chromatid exchange (SCE) frequency in transformed human fibroblast cell lines. Geneticin and hygromycin were both found to increase SCE frequency in all cell lines examined, including a cell line derived from a patient with Bloom syndrome, a disorder exhibiting an elevated spontaneous SCE frequency. Induction was seen to occur in a dose‐responsive manner and was also observed in cells expressing the resistance genes that inactivate the cellular toxicity of these antibiotics. The implications of these findings for somatic cell genetics and for human gene therapy protocols are discussed. © 1993 Wiley‐Liss, Inc.
In vitro cytotoxic and cell transforming activities exerted by the pesticides cyanazine, dithianon, diflubenzuron, procymidone, and vinclozolin on BALB/c 3T3 cells
Authors: Perocco Paolo , Colacci Annamaria , Grilli Sandro 
Published: February 2007

AbstractCytotoxic and cell transforming activities of the pesticides cyanazine, diflubenzuron, dithianon, procymidone, and vinclozolin were investigated in vitro by utilizing the BALB/c 3T3 cell transformation test performed in the presence or in the absence of S‐9 mix as an exogenous bioactivation system for the chemicals. All the assayed pesticides were cytotoxic in the absence of S‐9 mix, whereas only dithianon exerted cytotoxic effects in the presence of metabolic activation. All the chemicals tested did induce BALB/c 3T3 cell transformation, to a various extent, in the absence of S‐9 mix. Cell transforming ability of cyanazine and diflubenzuron was not detectable in the presence of S‐9. © 1993 Wiley‐Liss, Inc.
Selective aflatoxin B1‐induced sister chromatid exchanges and cytotoxicity in differentiating B and T lymphocytes in vivo
Authors: Potchinsky Merle B. , Bloom Stephen E. 
Published: February 2007

AbstractThe purpose of this study was to assess the genotoxic and cytotoxic effects of the fungal metabolite aflatoxin B1 (AfB1) on the developing immune system of the chick embryo, a model in vivo system. Of particular interest was the assessment of AfB1 ‐mediated selective toxicity toward developing B lymphocytes as compared to T lymphocytes. In vivo bromodeoxyuridine (BrdU) labelling of DNA was used to detect the induction of sister chromatid exchanges (SCE) in lymphocytes and to assess the progression of these cells through successive cell cycles. Cytotoxicity was also assessed by studying the entrance and maintenance of cells in mitosis (mitotic index). Graded doses of AfB1 (1.09–17.4 μ/g embryo) were applied to chick embryos of 18 days of incubation (Dl). Embryos also received two doses of BrdU at 3 mg/200 μ (3 hr apart) to provide continuous labelling of B and T lymphocyte replicating DNA. B and T lymphocytes were harvested 20 hr post‐AfB1/BrdU exposure from the bursa and thymus, respectively, and were processed for cytogenetic analyses. AfB1 induced dose‐related increases in SCE in B lymphocytes; this induction was 6‐ to 8‐fold that of controls at the higher doses tested, AfB1 ‐mediated induction of SCE in T cells was just 2‐fold that of controls at the highest dose tested. AfB1 reduced the progression of B cells and to a lesser extent T ceels through successive rounds of replication. Furthermore, AfB1 dramatically reduced the mitotic index of B cells but not of T cells. These data indicate both selective genotoxicity and cytotoxicity of AfB1 toward B cells in the late stage embryo. © 1993 Wiley‐Liss, Inc.
How much do we know about spontaneous human mutation rates?
Authors: Crow James F. 
Published: February 2007

AbstractThe much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes on the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane [Ann Eugen 13:262–271, 1947] in his classical study of X‐linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate.The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm, and may be considerably higher. The great mutation load implied by a rate of ≈ 1 per zygote can be greatly ameliorated by quasi‐truncation selection.Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 102 new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known.Statistical evidence in Drosophila shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50–100 generations. © 1993 Wiley‐Liss, Inc.
Induction of micronuclei by bleomycin in G0 human lymphocytes: I. Dose‐response and distribution
Authors: Hoffmann George R. , Colyer Shirley P. , Littlefield L. Gayle 
Published: February 2007

AbstractThe cytokinesis‐block micronucleus assay was used to investigate the induction of chromosomal damage by bleomycin in G0 human lymphocytes. A dose‐dependent increase in the frequency of micronuclei was observed in binucleate cells, and the frequency approached 0.5 micronuclei per cell at the highest dosage tested. The distribution of micronuclei among cells was overdispersed, rather than fitting a Poisson distribution. Even at the highest dosage, more than two‐thirds of the cells did not contain micronuclei, while some cells were highly damaged, containing more than 4 micronuclei percell. © 1993 Wiley‐Liss, Inc.
Evaluation of a three‐exposure mouse bone marrow micronucleus protocol: Results with 49 chemicals
Authors: Shelby M. D. , Erexson G. L. , Hook G. J. , Tice R. R. 
Published: February 2007

AbstractForty‐nine chemicals were tested in a mouse bone marrow micronucleus test that employed three daily exposures by intraperitoneal injection. Bone marrow samples were obtained 24 hr following the final exposure. Twenty‐five rodent carcinogens and 24 noncarcinogens were selected randomly from the 44 carcinogens and 29 noncarcinogens used by Tennant et al. (Science 236:933–941, 1987) to evaluate the performance of four in vitro genetic toxicity tests. As in that study of in vitro tests, the micronucleus tests were conducted with coded chemicals and test results (positive or negative) were determined prior to decoding. This study was conducted as part of an effort to assess the ability of the micronucleus test to discriminate between rodent carcinogens and noncarcinogens and to determine its potential role, in combination with other short‐term tests, in identifying genotoxic chemicals that present a carcinogenic hazard.Nine chemicals were judged to be positive in the micronucleus test. This relatively low number of positive results, along with published and unpublished results from rodent micronucleus and chromosome aberration assays on several of these 49 chemicals, contributed to the conclusion that a single micronucleus test protocol is not adequate to detect all chemicals capable of inducing chromosomal damage in the bone marrow. However, a combination of two relatively simple assays such as the Salmonella and micronucleus tests can provide important information on the genetic toxicity of test chemicals and may provide guidance on the need for and the nature and extent of further toxicity studies. © 1993 Wiley‐Liss, Inc.
Structural relationships between mutagenicity, maximum tolerated dose, and carcinogenicity in rodents
Authors: Rosenkranz Herbert S. , Klopman Gilles 
Published: February 2007

AbstractThe CASE structure‐activity relational system was applied to a study of the structural bases of toxicity as expressed in the maximum tolerated dose (MTD) of a group of chemicals for which rodent carcinogenicity and mutagenicity data were also available. All of the results were obtained under the aegis of the U.S. National Toxicology Program. The analyses revealed that there was a structural basis for the MTD in mice and in rats and that these overlapped considerably. There was also some overlap between structural determinants of the MTD and of carcinogenicity in rodents but there was also a significant “antagonism” between such fragments; i.e., fragments associated with high toxicity (low MTD) were associated with lack of carcinogenicity and vice versa. The highest overlaps observed were between the structural determinant for a low MTD (i.e., high toxicity) and mutagenicity in Salmonella. © 1993 Wiley‐Liss, Inc.
DNA response to bleomycin in mammalian cells with variable degrees of chromatin condensation
Authors: Lopez‐Larraza Daniel M. , Bianchi Nestor O. 
Published: February 2007

AbstractBLM induces DNA degradation in living cells. We used CHO cells with maximal chromatin compactness (cells synchronized in metaphase), cells with chromatin decondensed by Na butyrate treatments, and control cells with normal chromatin condensation in order to analyze the correlation between chromatin compactness, DNA sensitivity to BLM, efficiency of repair of BLM‐induced DNA lesions, and cell viability. We found that the DNA sensitivity to BLM and the efficiency of DNA repair is inversely correlated with the degree of chromatin coiling. Cells with decondensed chromatin are those showing higher DNA sensitivity to BLM but also those having the best efficiency to mend the damage. Accordingly, these cells show an amount of residual DNA lesions and a curve of growth similar to that of control cells. The situation is just the opposite for metaphase cells. The DNA of these cells is more resistant to BLM, but the damage is poorly repaired. The final result is that BLM induces a higher concentration of residual DNA lesions and a lower viability in metaphase than in control cells. Our results suggest that chromatin structure influences the quantity and repairability of the BLM‐induced lesions, producing a higher incidence of double strand break in the DNA of cells with marked chromatin condensation. © 1993 Wiley‐Liss, Inc.
Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I. Communication: Examination for the induction of gene mutations using the ames salmonella/microsome test and the HGPRT test in V79 cells
Authors: Lang Rainer , Reimann Roland 
Published: February 2007

AbstractThe mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7‐epoxycyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclotriol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG‐PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix). © 1993 Wiley‐Liss, Inc.