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  • 1
    Electronic Resource
    Electronic Resource
    Mechanistic study on liver tumor promoting effects of piperonyl butoxide in rats (1998)
    Springer
    Archives of toxicology 72 (1998), S. 744-750 
    Details
    ISSN: 1432-0738
    Keywords: Key words Piperonyl butoxide ; Phenobarbital ; Hepatocarcinogenesis promoting mechanism ; Gap junctional intercellular communication ; Cell proliferating activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Piperonyl butoxide, alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene, is a widely used pesticide-synergist. Recently, results were reported indicating that piperonyl butoxide is a hepatocarcinogen in rat. Since the underlying mechanism was not elucidated, we examined the effects on rat liver cells in detail. For this purpose male F344 rats were administered piperonyl butoxide mixed in the diet at concentrations of 0 (negative control), 0.05, 0.2 or 2% for 2 days, 1, 2, and 4 weeks. As a positive control, phenobarbital was administered to rats for up to 4 weeks as a 0.1% solution in the drinking water. Increased liver weight, centrilobular hepatocellular hypertrophy due to increased smooth endoplasmic reticulum, decreased numbers and areas of connexin 32-positive spots per hepatocyte, and increased cell proliferation were observed in rats treated with 0.2 and 2% piperonyl butoxide. Similar results were obtained for 0.1% phenobarbital treated rats. Hepatocellular necrosis suggestive of hepatotoxicity was also observed in the 2% piperonyl butoxide group. These results indicate that the promoting mechanism of piperonyl butoxide in hepatocarcinogenesis is similar to that of phenobarbital, involving an ability to induce CYP isoenzymes and inhibit gap junctional intercellular communication. In addition, increased cell proliferation following hepatocellular necrosis may also play a role at high doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050569
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  • 2
    Electronic Resource
    Electronic Resource
    Involvement of apoptosis in the rat germ cell degeneration induced by nitrobenzene (1998)
    Springer
    Archives of toxicology 72 (1998), S. 296-302 
    Details
    ISSN: 1432-0738
    Keywords: Key words Nitrobenzene ; Apoptosis ; Testicular toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nitrobenezene (NB) produces germ cell degeneration, especially of spermatocytes in rats. To examine the possible involvement of apoptosis in this process, the extent and nature of nuclear DNA fragmentation after NB dosing were assessed using both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and DNA gel electrophoresis, in addition to conventional histological and electron microscopic procedures. Adult Sprague Dawley rats were treated with a single oral dose of NB (250 mg/kg) and euthanized subsequently at 6, 12, and 24 h and 2, 3, 5, and 7 days. The earliest morphological signs of germ cell degeneration in testes were found in pachytene spermatocytes 24 h after dosing. Electron micrographs of degenerating spermatocytes showed marked nuclear chromatin condensation at the nuclear periphery and crowding of cytoplasmic constituents, which are characteristic of apoptosis. Coincident with the appearance of such morphological changes, degenerating spermatocytes contained fragmented DNA as revealed by TUNEL. The presence of DNA laddering, a hallmark of apoptosis on gel electrophoresis, was first apparent and most prominent at 24 h, gradually becoming less detectable. No such changes were observed up to 12 h after dosing or in control animals. These results demonstrated unequivocal involvement of apoptosis in the induction of germ cell degeneration caused by NB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050505
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  • 3
    Electronic Resource
    Electronic Resource
    Morphometric and immunohistochemical studies on atrophic changes in lympho-hematopoietic organs of rats treated with piperonyl butoxide or subjected to dietary restriction (1996)
    Springer
    Archives of toxicology 70 (1996), S. 809-814 
    Details
    ISSN: 1432-0738
    Keywords: Key words Piperonyl butoxide ; Diet restriction ; Atrophy of lympho-hematopoietic tissues ; Immunohistochemistry of T/B lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Changes observed in lympho-hematopoietic organs in rats given piperonyl butoxide may be attributable either to direct toxic effects or to undernutrition. Male F344 rats were therefore fed diet containing 2.5% piperonyl butoxide or subjected to a 64% restriction of food intake for 2 weeks. Marked inhibition of body weight gain, decreased white blood cell count, depletion of T/B lymphocytes in lymphoid tissues, hypoplasia of the bone marrow, and decreased proliferating cell nuclear antigen (PCNA) labeling indices in these tissues were seen in both dietary restriction and 2.5% piperonyl butoxide groups. The depletion of T lymphocytes in the thymus and spleen was stronger in the 2.5% piperonyl butoxide group, as indicated by PCNA labeling indices and image analysis of T lymphocyte areas of the spleen, however, the toxicological profile observed for the chemically treated group was essentially the same as for animals on the restricted diet. These results suggest that the lympho-hematopoietic findings in rats receiving 2.5% piperonyl butoxide are probably due to undernutrition resulting from a reduced food intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050343
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  • 4
    Electronic Resource
    Electronic Resource
    Ultrastructural changes in motor endplates of the lumbrical muscles of rats induced by a microsomal Ca2+ ATPase inhibitor, 2,5-di(tert-butyl)-1,4-hydroquinone (1997)
    Springer
    Archives of toxicology 72 (1997), S. 115-118 
    Details
    ISSN: 1432-0738
    Keywords: Key words 2 ; 5-di(tert-butyl)-1 ; 4-Hydroquinone ; Ca2+ ATPase inhibitor ; Neurotoxicity ; Ultrastructure ; Motor endplate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female Wistar rats were treated orally for 5 days with 80 mg/kg body weight of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), a microsomal Ca2+ ATPase inhibitor. Motor endplates of the lumbrical muscles were examined by light and electron microscopy. There was a decrease in body weight in the treated rats from the first day after administration, and toxic signs appeared after the third day, such as adoption of a prone position, salivation, lacrymation, and an abnormal gait and/or muscle weakness. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles as well as other peripheral nerves of hind legs of the treated rats killed 1 day after the last DTBHQ treatment. Ultrastructurally, neurotoxicity characterized by loss of synaptic vesicles and mitochondria in the motor endplates, and by destruction of the motor terminals was detected in the lumbrical muscles of the treated rats. These results strongly indicate that DTBHQ targets the motor endplates in the rat lumbrical muscles and suggest that the resultant damage is responsible for the appearance of neurological signs, such as an abnormal gait and loss of muscle control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050477
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  • 5
    Electronic Resource
    Electronic Resource
    Time course of ultrastructural changes and immunoelectron microscopic localization of neurocalcin in motor endplates of the lumbrical muscles of rats given a single administration of 2,5-di(tert-butyl)-1,4-hydroquinone (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 109-116 
    Details
    ISSN: 1432-0533
    Keywords: Key words 2,5-Di(tert-butyl)-1,4-hydroquinone (DTBHQ) ; Wistar rat ; Motor endplate ; Lumbrical ¶muscle ; Neurocalcin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A time-course study of ultrastructural changes and immunoelectron microscopic localization of neurocalcin was performed on motor endplates of the lumbrical muscles of female Wistar rats given a single oral administration of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ) at a dose of 120 mg/kg. Toxic signs such as salivation and muscle weakness of the hind legs appeared from 3 h after DTBHQ administration. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles of the treated rats. At the ultrastructural level, neurotoxicity characterized by a decreases or loss of synaptic vesicles and mitochondria was observed after 24 h and at the 1-week time point, nerve endings had disappeared in some of the motor endplates, while many neurite nerve endings suggestive of early stage regeneration were apparent. After 6 weeks, newly formed reinnervated endplates were observed. Immunoelectron microscopically, the synaptic vesicle membranes were heavily labeled for neurocalcin in the control rats, but not at 24 h after DTBHQ treatment. Synaptic vesicle membranes in the DTBHQ group were weakly labeled at 1 week, but strongly at 6 weeks. The results strongly suggest that DTBHQ targets the motor endplates in the rat lumbrical muscles, causing depletion of neurocalcin in the synaptic vesicles followed by their loss.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007413
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  • 6
    Electronic Resource
    Electronic Resource
    Comparative studies of the toxicity of standard reference materials in various cytotoxicity tests and in vivo implantation tests (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Biomaterials 4 (1993), S. 153-156 
    Details
    ISSN: 1045-4861
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Polyurethane films that contained various amounts of zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) were prepared as standard reference materials (SRM). Using three cell lines of V79, L929, and Balb/3T3 cells, the cytotoxicity of the dithiocarbamates and the SRM films were compared by agar diffusion assay, filter diffusion assay, neutral red assay, cell growth assay, and colony assay. Among these in vitro cytotoxicity tests, colony assay was found to be the most sensitive method for detecting the cytotoxicity. The cytotoxic potentials of extracts from SRM films correlated well with the concentrations of ZDEC or ZDBC involved in SRM. When various rubber materials including SRM and surgical rubber latex materials were tested, cytotoxic potentials of these extracts were also correlated with the inflammatory tissue capsule thickness in short-term implantation tests. On the basis of these results, the SRM is judged to be useful for validating test sensitivity, and comparing the correlation between in vitro and in vivo responses. © 1993 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jab.770040206
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  • 7
    Electronic Resource
    Electronic Resource
    Determination of thiols and disulfides in normal rat tissues and hamster pancreas treated with N-nitrosobis(2-oxopropyl)amine using 4-(aminosulfonyl)-7-fluoro-2, 1,3-benzoxadiazole and ammonium 7-fluoro-2, 1,3-benzoxadiazole-4-sulfonate (1989)
    New York, NY : Wiley-Blackwell
    Biomedical Chromatography 3 (1989), S. 166-172 
    Details
    ISSN: 0269-3879
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Biological thiols and disulfides in rat and hamster tissues were simultaneously determined by HPLC-fluorescence detection using 4-(aminosulfonyl)-7-fluoro-2, 1,3-benzoxadiazole (ABD-F) and ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F). The coefficients of variation (CV) of the method for reduced glutathione (GSH) and oxidized glutathione (GSSG) in liver and for cysteine (CySH) and cystine (CySSCy) in kidney were less than 3.1%. In 11 tissues of Wistar rats (liver, spleen, heart, lung, stomach, bladder, ovary, uterus, adrenal, kidney and pancreas), only CySH, CySSCy, GSH and/or GSSG were detected. Other thiols and disulfides were at extremely low levels in all samples. Both concentrations of CySH and CySSCy in the livers of old rats (111 weeks old, F344) were significantly higher than those of young rats (8 weeks old) (CySH, 0.246 ± 0.099 vs 0.130 ± 0.020 μmol/g; CySSCy, 0.051 ± 0.027 vs 0.013 ± 0.002 μmol/g). Administration of N-nitrosobis(2-oxopropyl)amine (BOP), a selective carcinogen of hamster pancreatic cancer, to Syrian golden hamsters (38 weeks old) resulted in the increase in the pancreas of GSH to a level 19 times as high and of GSSG to a level 14 times as high as those in untreated hamsters (GSH, 1.173 ± 0.272 vs 0.062 ± 0.017 μmol/g; GSSG, 0.155 ± 0.063 vs 0.011 ± 0.001 μmol/g).
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bmc.1130030406
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  • 8
    Electronic Resource
    Electronic Resource
    Rabbit eye irritation caused by wearing toxic contact lenses and their cytotoxicities: In vivo/in vitro correlation study using standard reference materials (1993)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 27 (1993), S. 885-893 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To clarify the relationship between eye irritancy and cytotoxic potential induced by irritant materials, we made lenses coated with standard reference materials (SRMs) prepared from various amounts of zinc diethyldithiocar-bamate (ZDEC) and polyurethane (PU).Zinc diethyldithiocarbamate was classified as a mild irritant by the Draize eye irritation test. When ZDECSRM coated contact lenses were applied to rabbit eyes, Draize scores increased in proportion to both the ZDEC and PU concentrations used for coating. Furthermore, correlation with the cytotoxic potential (γ = -0.93) was better than with lactate dehydrogenase (LDH) activities of tears from rabbit eyes wearing these coated lenses (γ = 0.78). In conclusion, in vivo eye irritancy induced by wearing lenses could be estimated quantitatively with the cytotoxic potentials using a colony assay. Further-more, we could compare different sensitivities caused by the same set of SRMs among three different sites of tissue. As a result, the order of sensitivity was eye 〉 muscle ≫ skin. © 1993 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.820270707
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  • 9
    Electronic Resource
    Electronic Resource
    Comparative studies by cell culture and in vivo implantation test on the toxicity of natural rubber latex materials (1992)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 26 (1992), S. 339-356 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Colony assay using V79 cells, the agar diffusion assay with L929 cells, and the 7-day rabbit muscle implantation test were employed to evaluate the cytotoxicity and tissue toxicity of natural rubber latex (NRL) materials. The in vivo implantation test showed that, among 13 histological parameters, thickness of inflammatory layer was the most useful index to evaluate tissue responses quantitatively. A comparison of the in vivo and in nitro parameters revealed the following correlations between the thickness of the inflammatory layer and cytotoxicity indices: Colony assay of the extracts, IC50: r = 0.80; Agar diffusion assay, Zone index: r = 0.73; Lysis index: r = 0.61. From these results, it appears that the colony assay provides a more reliable prediction of the tissue response than the agar diffusion assay.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.820260306
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