bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary evaluation of treatment and selection conditions which affect expression of anthracycline mutagenicity in Salmonella typhimurium and a diploid human lymphoblast cell line
Authors: Thomas Harvey F. 
Published: October 2006

AbstractMutagenic potency in the Ames Salmonella test is an important endpoint that can be influenced by biological and technical factors. The ranking of mutagenic activity of a series of anthracyclines was measured using different conditions of exposure and mutation selection. A 20 min preincubation treatment version of the Ames test using a 0.2–2.0 μg/ml (0.36–3.60 nM/ml) dose range of each of the anthracyclines Adriamycin, Daunomycin, Carminomycin, 4′‐O‐methyldoxorubicin and 4‐demethoxydoxorubicin confirmed the order of mutagenic potency seen with the same compounds under direct plating conditions. Preincubation results also confirm direct‐plating results by showing the greater sensitivity of selection to His+ reversion over 8‐azaguanine resistance to anthracycline mutagenicity. However, the order of mutagenic potency was changed by lengthening the preincubation treatment time to 2 h or reducing the population density of the treated cell inoculum by ten fold. These results suggest that certain treatment conditions enable the treated cells to diminish the phenotypic expression of anthracycline mutagenicity. For comparative purposes, daunomycin and Adriamycin mutagenicity in response to 0.1–0.2 nM/ml and 0.1–0.3 nM/ml dose ranges, respectively, were assessed in a human cell culture system with 6‐thioguanine and 5‐trifluorothymidine forward mutation selection. A daunomycin dose of 0.1 nM/ml generated approximately 25‐fold and 20‐fold increases in mutant fraction with 6‐thioguanine and 5‐trifluorothymidine selections, respectively. Equivalent dosing with Adriamycin generated approximately a 4‐fold increase in mutant fraction with 6‐thioguanine selection and little or no increase with 5‐trifluothymidine selection. Maximum increase in expression of mutant fraction within the anthracycline treated populations of cells occurred with a 10 day expression time. Plating for clone forming ability on the day of treatment showed that a standard 0.1 nM/ml treatment dose reduced cloning efficiency of the daunomycin treated cells by 90% and reduced the clone forming ability of the Adriamycin treated cells by 30%.
The post‐natal fate of supernumerary ribs in rat teratogenicity studies
Authors: Wickramaratne G. A. 
Published: October 2006

AbstractA common occurrence in rat teratology studies, supernumerary ribs, have been considered to be indicative of teratogenicity by some authors but not to be so indicative by others. As a teratogenic event is, by definition a permanent change, a study to follow the fate of supernumerary ribs in the development to adulthood of the rat was undertaken. An established teratogen in the rat, aspirin, was used to increase the frequency of supernumerary ribs. Even though aspirin treatment of the dams doubled the initial frequency of supernumerary ribs the results show that over the first 60 days post‐partum their frequency in both control and treated groups decline to essentially zero. This decline in frequency of supernumerary ribs is complemented by an increase in the proportion of foetuses with a fully developed transverse process on the first lumbar vertebra. The proposal that supernumerary ribs in the rat are a result of developmental delays in a labile region of the axial skeleton and not a manifestation of a teratogenic event is presented.
Evaluation of the division arrest method of the CHO/HGPRT mutation assay
Authors: Oshiro Y. , Balwierz P. S. , Piper C. E. 
Published: October 2006

AbstractWe have evaluated the division arrest method of the CHO/HGPRT mutation assay following the procedure described by O'Neill et al. Environ. Mutagen. 4, 421–434 (1982). This method simplifies the culture manipulations required during the expression period and can be readily adopted for screening mutagenic compounds. The mutation frequencies derived from the subculture method and the division arrest (no subculture) method after treatment of CHO‐K1BH4 cells with ethyl methanesulfonate were similar at all concentrations. The background mutation frequencies observed in the medium and solvent (0.5% DMSO) controls ranged from 0 to 9 colonies per 1 × 106 cells. Twenty to 24 h treatments, using the direct‐acting compounds ethyl methanesulfonate, N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, ICR‐191 acridine, 5‐Bromo‐2′‐deoxyuridine, mitomycin C and high concentrations of thymidine produced positive mutagenic responses, while 2′‐deoxyuridine and trifluorothymidine gave negative responses. Four‐h treatments with Benzo[a]pyrene, diethylnitrosamine, 2−acetylaminofluorene, 3‐methylcholanthrene and 2‐aminoanthracene in the presence of S9 also produced positive results. Anthracene, fluorene and pyrene with S9 were negative. However we found that a toxic, non‐mutagenic compound (anthracene) can yield sporadic increases in mutation frequencies (1 out of 10 replicates). Overall, our results indicate that the division arrest method of the CHO/HGPRT mutation assay can be reliably used for routine screening.
Assessment of hepatic function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association
Authors: Woodman D. D. 
Published: October 2006

AbstractThere are a wide variety of laboratory tests available to assess damage to and functional impairment of the liver, though the effectiveness of these tests varies greatly depending upon the type of damage and the animal species involved.Species differences in tissue localization, metabolism, specificity and sensitivity of parameters relating to the liver influence the choice of tests. Some tests can be applied usefully to most animal species while others may be highly specific in one species but show very low discriminatory potential in others.The tests available, and their use in veterinary and toxicological investigations have been reviewed in the light of current practice in the U.K.
Prevention of cadmium‐induced effects on regional glutathione status of rat brain by vitamin E
Authors: Shukla Girja S. , Srivastava R. S. , Chandra S. V. 
Published: October 2006

AbstractThe effect of vitamin E on the cadmium‐induced changes of glutathione metabolism was investigated in different brain regions. Daily intraperitoneal injection of cadmium (0.4 mg/kg) for 30 days significantly decreased the concentration of reduced glutathione (GSH), and the activities of glutathione reductase (GR) and glucose‐6‐phosphate dehydrogenase (GPDH) in the cerebellum, cerebral hemispheres and brain stem of rats. Cadmium elevated the levels of oxidized glutathione (GSSG) in cerebellum and cerebral hemisphere regions only, while the GSH/GSSG ratio decreased in all three brain regions. The only effect of intramuscular injections of vitamin E (5 mg/kg) given on alternate days for 30 days was a slight increase in GSH and GR in the cerebral hemispheres. The simultaneous administration of vitamin E and cadmium prevented cadmium‐induced changes in GSH and GSSG levels and in the GSH/GSSG ratio, but the cerebellar GSH remained lowered. Furthermore, vitamin E, with the exception of GR in the cerebral hemispheres, did not prevent cadmium‐induced changes in enzyme activities. As the simultaneous injections of vitamin E reduced cadmium‐induced alterations in glutathione concentration without having any appreciable effect on the activity of related enzymes, it is suggested that the preventive effect of vitamin E is mediated through its antioxidative effect, saving GSH from oxidative destruction in the brain of cadmium‐exposed rats.
A protocol to evaluate the fibrogenic potential of inhaled materials
Authors: Bennett I. P. , Pigott G. H. , Isaacs K. 
Published: October 2006

AbstractA protocol to provide a more rapid assessment of the fibrogenic potential of an inhaled particulate has been developed. Young rats are exposed nose‐only for 6 h/day, 7 days a week for 28 days to a respirable aerosol of the test compound. After exposure the rats are kept for up to 1 year, followed by histopathological assessment of the lung. Interim sacrifices could allow an estimate of the rate and severity of the development of any fibrogenic lesion.The protocol has been evaluated for chrysotile asbestos, α‐quartz and titanium dioxide using rats of both sexes and two different ages at first exposure. The results indicate that there are no significant differences in either the rate, type or extent of lesion provoked by a 28‐day exposure period when compared with the more conventional 1‐year exposure period studies. It can be concluded that neither sex nor age at first exposure cause any biologically significant differences in response, although young rats would be used in practice. Only one sex need be investigated.The protocol offers considerable benefits over conventional inhalation studies for fibrogenicity (where a 1‐year exposure period followed by a further 1‐year holding period is usual) by virtue of time, specificity (in the absence of continued exposure the development of any lesion can be studied free from initial inflammatory response) and cost, and could be incorporated into a standard subacute inhalation study design.The results obtained are also of more physiological relevance than studies based on intratracheal instillation.
Methodological aspects of the determination of the acute inhalation toxicity of spray‐can ingredients
Authors: Pauluhn J. , Machemer L. , Kimmerle G. , Eben A. 
Published: October 2006

AbstractSpray‐can ingredients, if liberated in confined spaces, are potential health hazards for man. Thus, appropriate inhalation toxicity studies have to be performed in accordance with internationally recognized guidelines, e.g. the US Environmental Protection Agency: Federal Insecticide, Fungicide and Rodenticide Act (FIFRA no. 81–3) or OECD no. 403.One of the essential requirements of such guidelines is that test animals (preferably rats) be exposed to a steady‐state concentration in a dynamic inhalation chamber for at least 4 hours. This is not easy to achieve with vapours released from a pressurized spray‐can.The method described here makes it possible to expose experimental animals in an inhalation chamber to a steady‐state concentration of intermittently released spray jets of constant doses per jet. Animal experiments and theoretical considerations (computer simulations) have shown that the method presented allows an up‐to‐date determination of the acute inhalation toxicity of spray‐can ingredients.
Effect of cimetidine on hepatic biochemical changes, liver toxicity and major urinary metabolite excretion of trichloroethylene in rats
Authors: Landriault Helene , Sirois Gerard , Chakrabarti Saroj , Cote Michel G. 
Published: October 2006

AbstractThe effects of cimetidine (CIM) (an inhibitor of the hepatic microsomal monooxygenase system) on the metabolism and hepatotoxicity of trichloroethylene (TRI) were studied in male Sprague‐Dawley rats. Rats were given three doses of 120 mg/kg i.p. (low‐dose regimen) of CIM at 0, 6 and 11 h for 1 day, or ten doses of 200 mg/kg (high‐dose regimen) at 8, 11, 14 and 17 h for 2 days and 8 and 11 h on 3rd day. Trichloroethylene (0.5 or 0.65 ml/kg) was administered i.p. 1 h after 2nd dose (low‐dose regimen) or 9th dose (high‐dose regimen) of CIM. In the low‐dose regimen study, the activity of hepatic microsomal aminopyrine N‐demethylase was decreased 1 and 5 h after the second dose and 7 h after the third dose of CIM, but became normal 20 h after the last dose. The cytochrome P‐450 content and the activities of aniline hydroxylase and epoxide hydratase remained unchanged. Trichloroethylene at both dose levels produced liver toxicity, as verified by increase in activities of SDH and SGPT as well as by liver histology. Cimetidine alone had no such effect. An apparent reduction in TRI toxicity by CIM (at both dose regimens) could be observed histologically. The biochemical tests (SDH and SGPT) corroborated the histological changes only when TRI was given at a dose of 0.5 ml/kg combined with a high‐dose regimen of CIM. Cimetidine at both dose regimens had a tendency to decrease the in vivo metabolism of TRI. These results therefore indicate that CIM may have a short‐lived inhibitory effect on the hepatic mixed‐function oxidase system, resulting in some protective effect on TRI hepatotoxicity.
Toxicokinetics of ochratoxin A in several species and its plasma‐binding properties
Authors: Hagelberg Sigrid , Hult Karl , Fuchs Radovan 
Published: October 2006

AbstractThe toxicokinetic profile of ochratoxin A was studied after the oral or intravenous administration of 50 ng/g b.w. to fish, quail, mouse, rat and monkey. The elimination half‐life varied from 0.68 h after oral administration to fish, up to 840 h after intravenous administration to monkey. The distribution volume ranged from 57 ml/ kg in fish to 1500 ml/kg in quail. The plasma clearance was most rapid in quail and fish, 72 and 58 ml/kg·h, respectively, while it was only 0.17 ml/kg·h in monkey. The bioavailability was as low as 1.6% in fish but as high as 97% in mouse.The binding abilities of ochratoxin A to plasma proteins were also studied. From these data we calculated the free fraction of toxin in plasma, which we found to be < 0.2% in all species investigated (including man) except fish.A similar but smaller investigation on the toxicokinetics and binding properties of ochratoxin B was also performed. Ochratoxin B was more readily eliminated and had a lower affinity for plasma protens, which partly may explain its lower toxicity.
A combined testing protocol for assessing genotoxicity in individual animals: Application to environmental toxicology
Authors: Harper Barbara L. , Ward Jonathan B. , Ramanujam V. M. Sadagopa , Ammenheuser Marinel M. , Au William W. , Moslen Mary Treinen , Legator Marvin S. 
Published: October 2006

AbstractA multiple end‐point approach to assessing genetic toxicity (the combined testing protocol, CTP) was evaluated in male and female CD‐1 mice exposed subacutely (3 and 6 weeks) to low levels of a custom‐blended gas mixture (epichlorohydrin, benzene, chloroprene and xylene, at 50, 100, 100, and 100 ppb, respectively, as the low dose, with concentration levels 10‐fold and 100‐fold higher as the intermediate and high doses, or 0.1, 1 and 10 ppm of benzene). Urine mutagenicity was tested in the Salmonella/microsome assay, chromosome aberrations were examined in bone marrow and spleen lymphocytes, micronuclei were measured in bone marrow and peripheral erythrocytes, and cytochrome P450 and glutathione S‐transferases were measured in the liver. Structural aberrations in alveolar macrophages and spermatocytes, and thioguanine resistance in spleen lymphocytes were examined for their suitability for incorporation into the overall protocol.Spleen lymphocytes were the most sensitive indicator cells, and showed a dose‐related increase (P<0.01) in structural chromosome aberrations and in cytotoxicity after 6 weeks of exposure. Analysis of micronucleus formation and metaphase aberrations in the bone marrow, and micronuclei in peripheral erythrocytes showed an overall statistically non‐significant but positive trend at the high dose. No mutagenicity was detected in pooled urine samples. Liver microsomal cytochrome P450 was not increased, but cytosolic glutathione S‐transferases were significantly increased in a dose‐related manner. Since the probability of detecting a genotoxic effect increases with the number of endpoints and tissues examined, this approach should be applicable to many situations without having to perform separate experiments for each tissue examined. The multiple endpoints evaluated and the flexibility of the CTP with respect to which endpoints are included, plus the reduction in experimental variability, give it advantages over batteries of separate assays.
Cadmium toxicity and bioantioxidants: Status of vitamin E and ascorbic acid of selected organs in rat
Authors: Shukla Girja S. , Chandra S. V. 
Published: October 2006

AbstractEffects of i.p. administered cadmium acetate (Cd, 0.4 mg/kg) was studied on the levels of vitamin E and ascorbic acid in different brain regions, liver, kidney, testis, RBC and plasma at 15, 30 and 60 days intervals in male albino rats (45 ± 5 g). Exposure to Cd for 15 days decreased the levels of vitamin E significantly in the liver and testis only, while 30 days of treatment resulted in a signifcant decline in cerebellum, cerebral cortex, corpus striatum, mid‐brain + hypothalamus, and plasma. Cadmium administration for 60 days caused a decrease in vitamin E in all tissues. Furthermore, a duration‐dependent decrease in hepatic ascorbic acid levels was noticed. The implications of these results are discussed.
Relative metabolism of quinones to semiquinone radicals in xanthine oxidase system
Authors: Lewis David C. , Shibamoto Takayuki 
Published: October 2006

AbstractRates of enzymatic single‐electron reduction of some myotoxc quinones to semiquinone metabolites in an in vitro xanthine oxidase/hypoxanthine/catalase system varied widely. Naphthoquinones, especially juglone, were found to undergo rapid single‐electron reduction. Benzoquinones and benzoquinoneimines, as well as phenanthrene‐9,10‐quinone, benzo[a]pyrene‐3,6‐quinone, and diethylstilbestrolquinone, were also actively reduced. The anthraquinones danthron, doxorubicin and emodin were poorly metabolized in this system. N‐Acetylcysteine inhibited quinone‐stimulated cytochrome C reduction at high concentrations. The results of this study are discussed with respect to cytotoxicity and mutagenicity of selected quinones.
Bioreactivity of intratracheally administered slate dust in rats: Incorporation of 14C‐acetate into lung lipids
Authors: Khan M. Firoze , Ali Shahid , Rahman Qamar 
Published: October 2006

AbstractThe effect of intratracheally instilled slate dust on the phospholipid profile, and 14C‐acetate incorporation into the lipids of lung lavage, whole lung tissue and its subcellular fractions, has been studied in rats. The acellular fraction of lung lavage showed a decrease in the phospholipid content at 4 days and then an increase at 40 days of dust exposure, whereas the cellular fraction showed the reverse. The order of 14C‐acetate incorporation into total lipids and individual phospholipids showed a parallel trend. The rate of incorporation with total lipids of lung tissue was higher at the two stages of dust exposure and a similar pattern prevailed in the subceiiuiar fractions, i.e. mitochondrial, microsomal and cytosolic fraction. Acetate incorporation was highest in mitochondria, followed by the microsomes. An increase in the microsomal and mitochondrial cholesterol levels was also observed. There was no significant change in the solvent‐extracted 14C‐counts of whole plasma, trichloroacetic acid (TCA) precipitate and TCA supernatant of plasma. The results indicate that slate dust causes an enhanced synthesis of pulmonary surfactant and other lung lipids and, therefore, has an effect on the metabolism of type II alveolar epithelial cells.
Chlordecone (kepone®)‐potentiated carbon tetrachloride hepatotoxicity in partially hepatectomized rats — a histomorphometric study
Authors: Kodavanti Prasada Rao S. , Joshi Urmila M. , Mehendale Harihara M. , Lockard Virginia G. 
Published: October 2006

AbstractOur previous studies indicated the involvement of some unidentified mechanisms, apart from the bioactivation phenomenon, in chlordecone (CD)‐potentiated CCl4 hepatotoxicity and lethality. Recent studies revealed that hepatocellular regeneration is suppressed in CD + CCl4 toxicity. The present work is a continuation of our earlier work employing a partial hepatectomy model for stimulating hepatocellular division, in normal (N) or CD‐treated (10 ppm for 15 days) rats. Male Sprague‐Dawley rats maintained on an appropriate dietary protocol and undergoing sham (SH) or partial hepatectomies (PH) were employed. Hepatocellular regeneration was assessed by measuring the percentage mitotic figures and by autoradiography of liver sections from rats given 3H‐thymidine in vivo. Hepatotoxicity was assessed by examining liver sections for necrotic cells, swollen cells and cells having lipid droplets. CCl4 (100 μl kg−1)‐induced histopathological alterations in CD‐pretreated rats were significantly decreased in rats 2 days post‐PH (PH2) as compared to SH rats or rats 7 days post‐PH (PH7), indicating that amplification of CCl4 toxicity is significantly reduced when there is a greater regenerative activity. The percentage of mitoses as well as the percentage of labelled cells were significantly elevated at 2–6 h after CCl4 administration in N rats but remained suppressed in CD rats. In CD‐pretreated PH2 rats where the percentage of mitoses and the percentage of labelled cells were many‐fold greater when compared to SH or PH7 rats, a portion of the stimulated hepatocellular division decreased significantly at 2–6 h after CCl4 administration, but remained significantly greater when compared to basal level of regeneration. These results support our concept that suppression of hepatocellular regeneration is one of the events responsible, besides the bioactivation phenomenon, for the CD‐potentiated CCl4 hepatotoxicity.
Dose‐related proximal tubular dysfunction in male rats chronically exposed to lead
Authors: Vyskocil Adolf , Pancl Jan , Tusl Miloslav , Ettlerova Eva , Semecky Vladimir , Kašparová Lucie , Lauwerys Robert , Bernard Alfred 
Published: October 2006

AbstractMale Wistar rats were given 0.5 and 2% lead acetate in drinking water for 2 months, 1% lead acetate for 3 months and sodium acetate equimolar to 2% lead acetate for 3 months. Glucose, total proteins, lactate dehydrogenase (LDH), lysozyme and β2‐microglobulin (β2‐m) were measured in 24‐h urine every month. Kidney weight and histology were also examined.At the three doses, lead exposure produced a significant elevation of the kidney weight. No significant change in urinary parameters was observed in rats given 0.5% lead acetate. Exposure to 1% lead acetate increased the urinary excretion of β2‐m only.At the 2% lead acetate dose the elevation of β2‐m excretion was accompanied by an increased urinary output of glucose, total proteins, lysozyme and LDH. Observations of the kidneys by light microscopy were in agreement with these biochemical findings. The nephrotoxic effect of acetate was excluded by the lack of biochemical or histological effects of sodium acetate on the kidney. It is concluded that a proximal tubular dysfunction is induced in rats chronically exposed to high doses of lead.
The effect of 2,4‐dichlorophenol on growth and plasmidic β‐lactamase activity in Escherichia Coli
Authors: Espigares M. , Mariscal A. 
Published: October 2006

AbstractThe toxic effects of 2,4‐dichlorophenol on two strains of Escherichia coli harbouring plasmids with β‐lactamase activity were studied. The toxicant had a significant effect on growth at concentrations of 12 μg ml−1 for the JA 221 (pBR322) strain, as well as at 24 μg ml−1 for the J5‐3 (RP4) strain. β‐Lactamase production was affected at concentrations of 96 μg ml−1 in both strains. However, β‐lactamase production does not seem to constitute a reliable toxicity test in view of its variability and relatively low sensitivity.