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  • 1
    ISSN: 1432-0533
    Keywords: Key wordsγ-Diketone neuropathy ; Distal axonopathy ; 2 ; 5-Hexanedione ; Neurofilament ; Quail
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurotoxic effects caused by chronic exposure to 2,5-hexanedione (2,5-HD) were investigated in normal and neurofilament (NF)-deficient quail (Quv strain). These quail were given 175 mg/kg per day of 2,5-HD intraperitoneally for 24 weeks. Five of nine normal quail showed clumsy gait. They had NF-rich axonal swellings in the distal parts of the peripheral nerves, ventral and lateral funiculus of the cervical cord, and cerebellar peduncles. Axonal degeneration consisting of accumulation of mitochondria, vesicles, microtubules and dense bodies was found distal to the axonal swellings. Testicular atrophy appeared in two normal quail. In contrast, four of nine Quv quail showed systemic tonic convulsion, and died of respiratory paralysis within 6 days. No significant changes in the nervous system or testis of these four dead Quv quail. The five other Quv quail survived and did not show any neurological signs. Again, no significant changes were detected in the nervous system or testis of the surviving Quv quail. The present study revealed that distal axonal degeneration did not occur without NF accumulation. These results suggest that NF accumulation is an essential factor in the development of distal axonopathy in γ-diketone neuropathy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 463-469 
    ISSN: 1432-1335
    Keywords: KBrO3 ; KBr ; NaBrO3 ; α2u ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Accumulation of α2u and induction of cell proliferation were examined in kidneys of rats exposed to KBrO3, KBr or NaBrO3 in their drinking water. Hyaline droplets observed after KBrO3 or NaBrO3 administration to male rats were specifically immunostained for α2u. Increases in cell proliferation were found in the proximal tubules of male rats given KBrO3 or NaBrO3 but not KBr for 2, 4, and 8 weeks. No such change was evident in KBrO3-treated female rats or the distal tubules of any treated animal. The concordance between hyaline droplet accumulation and increased cell turnover suggests that KBrO3- and NaBrO3-induced cell replication in kidneys of male rats may result from α2u nephropathy. Considering the fact that KBrO3 has genotoxic potential involving oxidative stress, we hypothesize that the induced cell proliferation might predominantly play an additive role in its carcinogenesis. Furthermore, the present data, showing similar effects of NaBrO3 on the rat kidney, are of direct significance to its risk assessment.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0738
    Keywords: Key words Potassium bromate ; 8-Hydroxydeoxy guanosine ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been assumed that oxidative damage, including formation of 8-hydroxydeoxyguanosine (8-OHdG) adducts in kidney DNA due to potassium bromate (KBrO3), a renal carcinogen to both sexes of rats, is involved in its mechanisms of tumor induction. However, despite the presumed existence of a repair enzyme(s) for 8-OHdG, there have been no reports demonstrating the changes in adduct levels during medium- or long-term exposure. To elucidate the actual kinetics regarding this parameter during the early stages of KBrO3 carcinogenesis, we measured 8-OHdG levels in kidney DNA together with cell proliferation in renal tubules in both sexes of rats receiving KBrO3 at a dose of 500 ppm in the drinking water for 1, 2, 3, 4, and 13 weeks. Rapid elevation of 8-OHdG levels was noted in treated male rats which persisted until the end of the experiment. Increased cell proliferation in the proximal convoluted tubules was also observed throughout the experimental period, concomitant with 2-globulin accumulation. Increase in 8-OHdG levels in treated females first became apparent 3 weeks after the start of exposure, with cell proliferation only elevated at the 13-week time point. The present study, employing the same route and dose of KBrO3 known to cause tumors, strongly suggested the requirement of persistent increase of 8-OHdG for neoplastic conversion. Moreover, a clear sex difference in susceptibility to generation of oxidative stress in kidney DNA was found, in addition to 2-globulin-dependent variation in cell proliferation in the renal tubules.
    Type of Medium: Electronic Resource
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  • 4
    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
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  • 5
    ISSN: 1432-0738
    Keywords: Key wordsp-Dichlorobenzene ; 8-Oxodeoxyguanosine ; Cell proliferation ; Renal carcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p-Dichlorobenzene (pDCB) is a male rat kidney carcinogen believed to act through α2u-globulin nephropathy. Recent data on metabolism, however, suggest a potential for generating oxidative stress. To examine possible mechanisms of kidney carcinogenesis, pDCB was studied for ability to produce 8-oxodeoxyguanosine (8-oxodG) in kidney nuclear DNA and for initiating activity in a two-stage renal carcinogenesis model. F344 male rats were given pDCB by intragastric instillation, 5 days/week for 13 weeks at 300 mg/kg per day, which is a carcinogenic dose with chronic administration. To assess initiation after exposure, trisodium nitrilotriacetic acid (NTA), a kidney tumor promoter was given in the drinking water at 1000 ppm for 39 weeks. At the end of the exposure segment, pDCB did not produce an increase of 8-oxodG levels in the kidney nuclear DNA in contrast to potassium bromate (KBrO3). Following NTA promotion, no neoplastic lesions occurred in rats given pDCB, although diethylnitrosamine carcinogenesis was enhanced. Thus, pDCB did not produce oxidative DNA damage in the rat kidney or effect initiation of kidney carcinogenesis. These data suggest that oxidative stress is not involved in pDCB-induced renal carcinogenesis. The α2u-globulin-mediated chronic nephropathy probably acts as a promoter, not an initiation of renal carcinogenesis. Accordingly, pDCB is assessed to have no cancer hazard to humans who are not susceptible to the α2u-globulin nephropathy.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0738
    Keywords: Kidney ; Liver ; Cell proliferation ; Rat ; Mouse ; p-Dichlorobenzene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell proliferation in the kidneys and livers of rats and mice exposed short-term to p-dichlorobenzene (p-DCB) was evaluated by immunohistochemical measurement of bromodeoxyuridine (BrdU) incorporation into nuclei of DNA-synthesizing cells. p-DCB was given by gavage at two doses up to 600 mg/kg body weight for 4 days. The cumulative fraction of proliferating cells was increased in the proximal tubule epithelial cells of male rats at the high dose, but not at the low dose nor in females at either dose using gamma-glutamyl transferase reaction to identify tubular cells. Also, no increase in cell proliferation was found in mouse kidneys. The fractions of proliferating cells in the livers of rats and mice of both sexes were also increased. The increased cell proliferation in only male rat kidney and in the livers of mice of both sexes correlates with the reported carcinogenic effects of p-DCB in those tissues. However, the finding that p-DCB also induced cell proliferation in the livers of rats of both sexes, which were not a site of p-DCB-induced tumors in bioassays, and in female mice at the low dose, which was not affected by an increase in tumors, reveals a lack of concordance and indicates that acute induction of cell proliferation is not sufficient to lead to carcinogenesis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Two kinds of polyetherurethane (PEU), U-3 and U-8, were coated in thin layers on an ethylene-vinylalcohol copolymer (EVAL) film 0.1 mm thick. U-3 is a nonsegmented PEU prepared from 4,4′-diisocyanatodiphenylmethane (MDI) and poly(tetramethylene oxide) of Mn = 1,000 (PTMO 1000), and U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. The coating thicknesses were 0.0068 and 0.022 mm for U-3 and U-8, respectively. These coated films were implanted subcutaneously into rats and retrieved after various weeks. The coatings on the retrieved samples were dissolved in tetrahydrofuran (THF), and the average molecular weight (MW) was determined by injecting the THF solution into a gel permeation chromatograph. In the case of U-3, MW increased after 2 weeks, then decreased over the implantation period. After 10 weeks, U-3 almost disappeared from the base film. In the case of U-8, MW reached the maximum at 4 weeks postimplantation then decreased gradually over the implantation period. The rate and degree of MW change were greater in U-3 than in U-8. Here, we argue that, in the early stage, low molecular weight PTMO/MDI oligomers leached out from the PEUs to the inflammatory exudate to increase MW, and in the later stage macrophage attachment/activation had a role in the degradation of PEUs. The surface morphologic changes observed by scanning electron microscopy are also discussed. © 1994 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: In vivo degradation of polyetherurethanes (PEUs) was studied using two kinds of PEUs, U-3 and U-8, coated on a base film of ethylene/vinyl alcohol copolymer (EVAL). U-3 is a nonsegmented PEU prepared from 4,4′-diisocyanato-diphenylmethane (MDI) and poly(tetramethylene oxide) (PTMO 1000). U-8 is a segmented PEU prepared from MDI, PTMO 1000, and 1,4-butanediol. Previous studies of PEUs were conducted using gel permeation chromatography and scanning electron microscopy. In this study, the explanted materials were examined with contact angle measurement, ATR-FTIR, and nuclear magnetic resonance (NMR) spectroscopies. All data obtained by these methodologies indicate that the PTMO/MDI oligomers diffused to the material surface in the early stage of implantation. Then, the lowmolecular-weight fraction of the oligomers leached out from the surface to the exudate. Degradation became dominant after 2-4 weeks. In the case of PU-8, the PTMO fraction decreased approximately 35-40% from the surface at 24 weeks postimplantation. In the case of PU-3, the loss of coating material (U-3) on the base film (EVAL) was observed after 10 weeks. The PTMO fraction of the surface U-3 remained on EVAL at 6 weeks postimplantation, however, it was 64% of the initial material. The molecular weight of the U-3 remaining on EVAL also decreased. Degradation of U-3 occurred more rapidly than that of U-8. The data obtained with our materials were insufficient in determining evidence of oxidative degradation with IR or NMR spectra. © 1995 John Wiley & Sons, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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