Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Volume 2 , Issue 2
Showing 1-12 articles out of 12 articles from the selected issue
  • Atsushi Ichikawa, Misao Ichikawa
    1989 Volume 2 Issue 2 Pages 151-161
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    A variety of morphological changes in cells and tissues due to preparative procedures were compared at the electron microscopic level using specimens processed by immersion- and perfusion- methods of chemical fixation as well as quick freezing followed by freeze-substitution. The reality or artifact of some observations obtained from the materials processed by conventional chemical fixation, such as the so-called “intercellular interdigitation” of neighboring epithelial cells, open appearance of the lumen in the renal proximal convoluted tubules, the cytoarchitecture and secretory process of mucus-secreting cells, the morphological process of fusion and fission of biological membranes and others, is discussed by comparing the morphological observations obtained from the materials processed by conventional chemical fixation to those processed by quick freezing followed by freeze-substitution. The latter method is considered to be the most effective fixation method for preserving the cellular structures more closely in their living state.
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  • Kohichiro Ohtsubo
    1989 Volume 2 Issue 2 Pages 163-174
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    A sublethal dose of 140mg/kg b.w. of chaetochromin, a mycotoxin produced by Chaetomium spp, caused lesions in various organs characterized by rather slow-developing necrosis and repair in the ICR male mice. With 3 to 4 days of latent period, focal necrosis of the liver and myocardium and diffuse hematopoietic cell necrosis of the bone marrow were observed histologically. Necrosis also occurred in the spleen, lymph nodes, and thymus but intestinal epithelial cells were not affected. Electron microscopic examination of the heart revealed mitochondrial swelling and degeneration showing myelin-like figures at 3 days, focal and single cell necrosis with disruption of myofibrils at 7 or 8 days. After 11 days calcification developed in necrotic foci of the heart and liver, ensuing foreign body reaction up to 24 days. The bone marrow recovered with no sequelae by 14 to 24 days.
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  • Toshiharu Sakai, Satoshi Yoshida, Ryuhei Fujimoto, Takanori Hanada, Ya ...
    1989 Volume 2 Issue 2 Pages 175-179
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    Rats deprived of blood, amounting to about one percent of body weight, via orbital venous plexus phlebotomy for 2 weeks developed severe anemia. Their mean hematocrit value was 19%, and centrolobular liver cell necrosis was observed in animals with hematocrit value of 20% or less at the end of the study. It is obvious that the animals must have been in a severe anemic condition to develop liver cell necrosis. Thus, anemia should be considered as a causative factor of liver cell necrosis in toxicity studies in which the animals are in severe anemia attributable to drug administration.
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  • Akio Shimizu, Masaoki Harada, Tohru Inoue, Masayoshi Kanisawa
    1989 Volume 2 Issue 2 Pages 181-187
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    The cancer promoting effect of furfural (C4H3OCHO) was investigated using N-2-fluorenylacetamide (2-FAA) as an initiator. Male Wistar rats, 5 weeks old, were divided into four groups. One group was given three cycles of 0.03% 2-FAA, one cycle consisting of 3 weeks of 0.03% 2-FAA administration and 1 week of basal diet feeding, followed by 16 weeks of furfural administration (20ml/kg basal diet). The other three groups were given 2-FAA only, furfural only, or used as non-treated controls, respectively. Twenty-eight weeks after the end of furfural administration, the animals were killed and histopathological observations including GST-P immunostaining were made. There were no statistically significant differences between the animals given 2-FAA+furfural and the animals given 2-FAA only with regard to the proportion bearing hepatocellular carcinoma (HCC) and the proportion bearing neoplastic nodules. Also, there were no statistically significant differences in the numbers of HCC foci, neoplastic nodules, and GST-P-positive foci per unit area of liver. It is tentatively concluded that furfural does not exert a promoting effect on 2-FAA induced hepatocarcinogenesis in rats. As to our previous findings that furfural-induced hepatic cirrhosis enhanced 2-FAA hepatocarcinogenesis, it is suggested that the morphological distortion of the liver during cirrhotic change, rather than a direct effect of furfural, plays some role in chemical hepatocarcinogenesis.
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  • Teruo Suzuki, Hisako Tanaka, Tohru Obata
    1989 Volume 2 Issue 2 Pages 189-202
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    In order to study the nature and the significance of the appearance of membraneous conglomeration (Mc) of smooth-surfaced endoplasmic reticulum (SEr) in the proximal tubular cells (PTC) of the kidney, SD strain SPF male rats were given 150mg/kg/day of phenobarbital (PB group) and 40mg/kg/day of 3-methylcholanthrene (MC group) for 4 days, respectively. For controls, non-treated animals and animals only given normal saline or corn oil were used. Biochemical analyses and electron microscopic examinations revealed significantly increased microsomal P-450 not only in the liver but also in renal cortical tissue of MC- and PB group animals together with proliferation of SEr in the liver and of Mc in PTC of the kidney. Proliferation of Mc in PTC was found in all segments of S1, S2, and S3 but was more prominent in the MC group rather than in the PB group. In immunohistochemistry, reactions with MC-induced monoclonal antibodies APL1 and APH8 which are respectively specific for P-450c and P-450d, c were strongly positive in both liver cells and PTC of MC group animals. In PB group animals, however, reaction with PB induced monoclonal antibody APF3 which is specific for P-450b, c was strongly positive in the liver but almost negative in PTC of the kidney. These results indicate that proliferation of Mc in PTC of the kidney is a cellular reaction essentially corresponding to the similar change of hepatic parenchymal cells with induction of P-450 enzymes for metabolizing drugs or noxious chemical substances such as MC and PB.
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  • Hiroshi Maeda, Toshio Abe, Hiroaki Miyajima
    1989 Volume 2 Issue 2 Pages 203-212
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    Puromycin aminonucleoside (PAN) at a dose of 1.67mg/100 g body weight was injected subcutaneously for 10 days into male Sprague-Dawely rats. The mean urinary protein excretion of the PAN-treated rats was more than 80 times as much as that of the control rats. In light microscopy, swelling and vacuolation of glomerular epithelial cells, and slight thickening of mesangial area were found, but the glomerular basement membrane was not involved. Lysozyme binding was reduced in the lamina rara externa and interna of the glomerular basement membrane and the epithelial surface. Eight sorts of lectins were used to examine alterations in the oligosaccharide chain. Binding of Bauhinia purpurea (BPA) with the capillary wall was markedly increased in PAN-treated rats. The binding of Glycine max (SBA) showed a pattern similar to BPA, but the increment was much less. Thus the alteration of the oligosaccharide chains of the glomerular capillary wall might have a close relationship to the development of proteinuria in PAN-treated rats.
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  • Koichi Takada, Kazuo Yasuhara, Yukio Nakaji, Hamako Yoshimoto, Junko M ...
    1989 Volume 2 Issue 2 Pages 213-222
    Published: November 30, 1989
    Released: January 22, 2009
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    Groups of 50 male and 50 female ddY mice were fed commercial diet containing 0, 0.012, 0.06, 0.3, and 1.5% tris (2-chloroethyl) phosphate (TCEP) for 18 months. In both sexes fed 1.5% TCEP, body weight gain was apparently suppressed and mortality rates were clearly higher compared to other groups. After histopathological examination, the incidences of renal cell carcinomas and adenomas were significantly increased in males fed 1.5% TCEP. The incidences of hepatocellular adenomas were significantly high in the 0.3 and 1.5% groups of males. In females, significant increases were found in the incidences of papillomas and squamous cell carcinomas (combined) of the 1.5% group, and in those of leukemias of the 0.3 and 1.5% groups.
    Under the conditions of this study, orally administered TCEP was carcinogenic to ddY mice, causing significantly high incidences of tumors in the kidney and liver of male mice and in the forestomach and hematopoietic organ of female mice.
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  • Takesaburo Ogata, Tokuhiko Shibagaki, Hiroshi Kamma, Tomoyuki Yokose, ...
    1989 Volume 2 Issue 2 Pages 223-240
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    The alveolar damage produced by a variety of toxic agents, whether air-borne or blood-borne, progresses to a sequence of nonspecific changes histologically regarded as diffuse alveolar damage. Ultrastructurally, their alveolar damage can be divided into epithelial and endothelial type according to their target cells. The epithelial and endothelial type of alveolar damage was demonstrated in the experimental models of paraquat and monocrotaline toxicity, respectively. The two types of alveolar damage show different courses in the development of the sequent changes, which may influence the time courses and the patterns of final alveolar fibrosis. However, the endothelial type of alveolar damage may also induce secondary injury to the epithelial cells, so that the damage of this type finally becomes similar to that in the epithelial type. The mechanism of secondary epithelial damage was discussed on the basis of the antioxidation function of the lung. In many pneumotoxins, however, the detailed pathogenesis of alveolar changes remains to be clarified.
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  • Minro Watanabe, Hideaki Kikuchi, Ikuko Sagami, Hiroshi Fujii, Tetsuo O ...
    1989 Volume 2 Issue 2 Pages 241-251
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    Most chemical carcinogens and toxicants formed in our environment require metabolic activation or detoxification to exert their harmful effects or be rendered harmless, respectively, in their target cells and tissues. The major activation pathway is oxidative metabolism, usually catalyzed by cytochrome P-450-dependent monooxygenase systems. Multiple forms of cytochrome P-450 have been isolated and characterized from certain species of experimental animals. In this review we attempt to present a discussion of 1) specificity of catalytic activity in cytochrome P-450 enzymes in chemical carcinogenesis, 2) distribution of cytochrome P-450 enzymes in different species of experimental animals, 3) specificity of cytochrome-P-450 enzymes in extrahepatic tissues, and 4) genetic regulation in the susoeptibility to cancer in experimental animals and human. One of the important problems is to evaluate the role of extrahepatic cytochrome P-450 in chemical carcinogenesis and toxicity. We know some forms of cytochrome P-450 are highly localized in particular regions or cells, as for example, in non-ciliated bronchiolar (Clara) cells of the lung. Whether or not cytochrome P-450 enzymes and other drug metabolizing enzymes play significant roles in the expression of chemical toxicity in target tissues, may depend on the stability of biologically reactive intermediates mediated in vivo by the liver, the major organ for these enzymes. It is of interest that there is an apparent tissue difference in the expression of the cytochrome P-450IAl gene and in the inducibility of benzo [a] pyrene hydroxylation by 3-methyl-cholanthrene between lung and liver in Syrian golden hamsters. Whenever we attempt to postulate a process explaining the primary prophylaxis leading to chemical carcinogenesis in human, we have to deal with the question of which similarities of cytochrome P-450 and the related drug-metabolizing enzymes encountered in the animal model situations may extend to those of interest in the human populations at potential risk.
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  • Hiroshi Kuse, Kazunori Imaizumi, Isao Wada, Masaki Hori, Azusa Okaniwa
    1989 Volume 2 Issue 2 Pages 253-259
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
    Kanamycin (KM)-induced auditory disturbance in dogs was followed by time lapse recording of auditory brainstem response (ABR) and blood chemical examination. KM was administered subcutaneously to 6 beagle dogs 4 to 7-months of age at daily doses of 125, 250, and 500mg/kg for 13 to 71 times. At the end of the experiments the dogs were sacrificed and their kidneys and inner ears were examined histologically. KM-induced auditory disturbance at about 6, 500mg/kg of total dose in beagle dogs. Auditory disturbance induced by administration of 500mg/kg KM for 13 to 14 days to a dog was induced by sudden loss of ABR waves, when loss of pinna reflex was also noted in animals autopsied. Blood chemical examination revealed transient elevation of GOT, BUN, LDH, and CPK value. After recovery periods, in dogs treated with 125 and 250mg kg KM, the disorder of ABR remained unchanged. Histopathologically, loss of hair cells of the organ of Corti and degeneration of supporting cells were recognized at dose of 125, 250, and 500mg kg KM. Histological damage correlated well with the observed ABR changes. The present invesigation revealed usefulness of electrophysiological methods to detect ototoxicity in dogs.
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  • Kanji Yamasaki, Chitoshi Itakura
    1989 Volume 2 Issue 2 Pages 261-266
    Published: November 30, 1989
    Released: January 22, 2009
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    Histological and histochemical studies were carried out on the costal cartilage of Sprague-Dawley rats at 10, 18, 30, and 54 weeks of age. Histological changes were characterized by vacuolization, atrophy, enlargement or disappearance of chondrocytes, and loss of homogeneity of the matrix. These changes were seen from 10 weeks of age, and progressed with increasing age. On the other hand, proliferation of chondrocytes from the perichondrium was seen from 30 weeks of age. Acidic mucopolysaccharides decreased with increasing age, and increased in the area of chondrocyte proliferation described above.
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  • [in Japanese]
    1989 Volume 2 Issue 2 Pages 267
    Published: November 30, 1989
    Released: January 22, 2009
    JOURNALS FREE ACCESS
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