Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
14 巻, 1 号
選択された号の論文の14件中1~14を表示しています
Originals
  • Takeo Shimo, Junichi Katayama, Akemi Saito, Eisuke Morohashi, Yasuhiro ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 1
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Immunohistochemical investigations on the expression of PCNA, cyclin D1, and p53 were carried out on uterine proliferative lesions of heterozygous p53 deficient CBA mice [p53 (+/-) mice] given an intraperitoneal injection of 120 mg/kg body weight of N-ethyl-N-nitrosourea (ENU) followed by diet containing 1 or 2.5 ppm ethinylestradiol (EE) for 26 weeks. Histopathologically, uterine proliferative lesions were classified as endometrial stromal tumors (polyps and sarcomas), atypical hyperplasias (clear and basophilic cell types), an adenocarcinoma, and glandular hyperplasias. The PCNA labeling index (LI) for endometrial stromal tumors was very high in some areas of sarcomas in the ENU+EE groups, but very low elsewhere and in polyps, with significant differences. The PCNA LI for clear cell type atypical hyperplasias was also significantly greater than for glandular hyperplasias or basophilic cell type atypical hyperplasias. Values were comparable for each proliferative lesion between the ENU+2.5 ppm EE and ENU+1 ppm EE groups. In addition one adenocarcinoma with markedly high proliferation was seen with the higher dose of EE. Overexpression of cyclin D1 was also apparent in actively proliferating areas of stromal sarcomas and clear cell type atypical hyperplasia, percentages of positive cells being 67-100%. In contrast, p53 was only expressed in markedly proliferative areas of stromal sarcomas at percentages of 69 and 89 in the two groups. The present study indicates that cyclin D1 and p53 may play key roles in uterine transformation of proliferative lesions in p53 (+/-) mice.
  • Masanori Murakoshi, Rie Ikeda, Masashi Tagawa, Toshio Iwasaka, Takahar ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 9
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10 mg/kg for four years. Estrus was completely inhibited in the CMA-implanted animals. In contrast, all control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. Histopathlogically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in liver, adrenal, mammary gland, gallbladder, and implanted site. Furthermore, the intensity of staining and number of adrenocorticotropic hormone (ACTH)- and luteininzing hormone (LH)-positive cells in the pituitary sections of CMA-implanted animals were not different from the control animals. It was concluded, therefore, that subcutaneous implantation of CMA (10 mg/kg) is nearly equivalent to the minimal ovulation-suppressing dose.
  • Kazuo Hakoi, Taiji Hayashi, Kenji Irimura, Shuji Hayashi, Satoshi Suzu ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 13
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    DHG, a glycosaminoglycan extracted from the sea cucumber is known to show antithrombotic effects in animals and be a possible therapeutic agent for prevention of disseminated intravascular coagulation. In toxicology study, however, dose-dependent intracellular deposition of eosinophilic or basophilic droplets, and crystalloid substances were observed in the proximal tubular epithelial cells of the kidneys when male Sprague-Dawley rats were administered DHG daily for two weeks at the doses of 10, 100, and 200 mg/kg. In contrast to heparin, a glycosaminoglycan that has been reported to induced similar deposits which were identified to be composed of a hemoglobin-like substance using the alizarin red staining. The inclusions observed in rats given DHG were immunohistochemically positive for α2u-globulin. Moreover, the droplets showed metachromasia in toluidine blue staining, and negative for Hall's, Gmelin's, Schmol's tests, and alizarin red staining, but the crystalloids were positive for alizarin red staining. These results suggested that DHG-induced degeneration of proximal tubular epithelial cells in male rats is related to α2u-globulin accumulation.
  • Yoshimasa Okazaki, Kotaro Yamashita, Masato Sudo, Minoru Tsuchitani, I ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 19
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    This study was performed in order to identify the recovery from paralytic gait and hindlimb paralysis in rats that were treated once with 1000 mg/kg of aniline. Additionally, spongy change in the white matter of the spinal cord were chronologically examined in order to clarify the morphologic events in the lesions of the aniline-treated rats, which were killed on days 4, 8, 12, 15, 22, 30, and 60. Paralytic gait first appeared at day 8. The incidence of the paralytic gait and hindlimb paralysis increased in the following 4 days, and then decreased by day 19. Spongy change in the white matter of the spinal cord was first detected on day 8 in the histopathologic examination. The spongy state was due to splitting of the intraperiod line of the myelin sheath at the ultrastructural level. The incidence and severity of the lesions increased by day 12 or day 15, and then the spongy state repaired markedly by day 60. In the electron microscopic examination, the membranous aggregates in the cytoplasm of oligodendrocytes in the white matter of the spinal cord were detected on day 4, prior to the appearance of spongy change in this area. The immunoreactivity to anti-transferrin (Tf) antibody is an indicator of mature oligodendrocyte, metabolically supporting myelin. The decreased Tf-immunoreactivity of the oligodendrocytes was found in the aniline-treated rats that were killed on day 4. This result suggests the dysfunction of oligodendrocytes with respect to the myelin turnover. Remyelination in the lesions was apparent on day 22, according with the processes of the disappearance of membranous aggregates in the oligodendrocytes and the processes of the recovery of the Tf-immunoreactivity of the oligodendrocytes. Our results suggest that the possible primary target of aniline neurotoxicity is oligodendrocytes, and that the affected rats are able to recover spontaneously from this neurotoxicity.
  • Hirofumi Yuasa, Satoshi Yoneyama, Masao Ichinose, Kazumasa Miki, Tetsu ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 29
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Expression of cathepsin E in epithelial cells of the normal glandular stomach and small intestine, intestinal metaplasia, stomach and small intestinal tumors, was investigated in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Immunohistochemically, parietal cells were found to be moderately positive while surface mucous and pyloric gland cells demonstrated marked staining. Intestinal metaplastic glands in the stomach and normal small intestinal epithelial cells did not have any cathepsin E reactivity although some regenerative small intestinal epithelium proved positive. Histochemical staining for mucin demonstrated all stomach tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to be mainly comprised of gastric epithelial type cells (pyloric gland and surface mucous cells), with intestinal epithelial type cells (goblet and intestinal absorptive cells) being only occasional findings. Almost all of the gastric epithelial type cells showed cathepsin E reactivity in their cytoplasm while the intestinal epithelial cell type cells were mainly consisted of cathepsin E negative one like those in small intestinal cancers. Catepsin E may thus be a useful marker for cell differentiation of stomach tumors and their intestinalization. Cancers arising in the small intestine consisted of intestinal epithelial cell type cells, but no stomach tumors consisted predominantly of this type, so that there was no suggestion of any derivation from intestinal metaplasias in rats.
  • Akihiro Hagiwara, Kayoko Miyashita, Takumi Nakanishi, Masashi Sano, Se ...
    原稿種別: Original
    専門分野: None
    2001 年 14 巻 1 号 p. 37
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    The modifying effects of carrageenan administration on colonic carcinogenesis were investigated in male F344/DuCrj rats subcutaneously injected with 1,2-dimethylhydrazine dihydrochloride (DMH) 4 times at weekly intervals. Starting one week after the final injection of DMH, the rats were given carrageenan at dietary levels of 0, 1.25, 2.50, or 5.0% until week 36. Animals given cholic acid at a dietary level of 0.2%, served as a reference group. All rats were killed at the end of week 36, and the colons were carefully examined for preneoplastic and neoplastic lesions. No treatment related changes in clinical signs and body weights were found. Detailed histopathological examination did not demonstrate any enhancement by carrageenan of carcinogenesis with regard to the incidence of lesions in the colon. The results thus demonstrate that carrageenan does not possess any promoting activity at the highest dietary level of 5.0% for colorectal carcinogenesis under the present experimental conditions.
Short communication
  • Osamu Katsuta, Yuki Tomonari, Yoshimasa Okazaki, Makoto Kawamura, Kazu ...
    原稿種別: Short Communication
    専門分野: None
    2001 年 14 巻 1 号 p. 45
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Recently, a high incidence of naturally occurring Helicobacter pylori (H. pylori)-related gastritis was reported in a cynomolgus monkey colony (Reindel et al., 1999). We retrospectively examined 82 cynomolgus monkeys from three different countries. These monkeys were used in toxicological or pharmaceutical studies in our laboratory. Diffuse antral gastritis was observed in 49 of 58 (84%) animals of Group A in the Philippines, and two of 10 (20%) of Group C in Japan. In their antrum, the mucosal layer was thickened with lymphocytic and plasmacytic infiltration, and enlarged lymphoid follicles. However, no erosion or hemorrhage was seen in the lesions. H. pylori-like bacteria were detected by Warthin-Starry staining in almost all of the monkeys showing antral gastritis. No histological changes or H. pylori-like bacteria were detected in the animals of Group B in Indonesia. In conclusion, although the incidence of infection may be in part due to the breeder, natural infection of H. pylori was confirmed in cynomolgus monkeys. Thus, this species as well as rhesus monkeys may be useful in the study of H. pylori infection. Moreover, because of its high incidence, the colony in the Philippines may be suitable for an animal model, as it is comparable with natural infection in humans.
Case Report
  • Kiyonori Kai, Norihiro Sato, Atsushi Watanabe, Kazumi Shiraiwa, Shinic ...
    原稿種別: Case Report
    専門分野: None
    2001 年 14 巻 1 号 p. 51
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Polycystic lesions of kidney and liver were found in Crj:CD(SD) rats of 9 males and 6 females ranging in age from 5 to 57 weeks and were histopathologically or immunohistochemically investigated. Renal cysts were observed in the outer medulla at the beginning and confirmed to be dilatations of the collecting ducts by Dolichos biflorus agglutinin lectin histochemistry. At an advanced stage, the cysts expanded toward the cortex owing to dilatation of the collecting ducts and distal tubules, inflammatory cell infiltration, and fibrosis surrounding the cysts were observed additionally. The TUNEL assay revealed apoptotic cell death in the tubular epithelium of the cysts. Electron microscopy represented slightly thickened and laminated basement membranes of the cysts.The liver lesion at the beginning revealed slight dilatation of bile ducts and lymphatic ducts in Glisson's sheath. At the advanced stage, dilatation of bile ducts spread over the liver, proliferation of bile ducts, desquamation of the biliary epithelium, and fibrosis surroundings the bile ducts were observed in addition to the cystic lesions. The histological features of the cystic lesions were similar to those of human autosomal recessive polycystic kidney disease (PKD). None of the rat PKD models presented concurrently the biliary cysts. Therefore, these rats may be a potential model for human PKD and be useful for studying the correlation of the pathogenesis between the renal cysts and the biliary cyst.
Proceedings for Symposium “Toxic Changes of Endocrine Organs and Endocrine Disrupting Chemical” in the XVI Meeting of Japanese Society of Toxicologic Pathology
  • Kiyoshi Imai, R. Yoshiyuki Osamura
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 57
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
  • R. Yoshiyuki Osamura, Toshiki Iwasaka, Shinobu Umemura
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 59
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Recently, much has been focused on the potential for a wide range of chemicals to interact with the disruption of the endocrine system in humans and animals. Some of those chemicals have been implicated as endocrine disrupting chemicals (EDCs). We represent this review that the current endocrine systems including of molecular biology and effects of EDCs are discussed, as examples pituitary and mammary gland. Alterations to the endocrine environment caused by EDCs may occur through interference with the synthesis, secretion, transport, binding, action, or elimination of natural hormones responsible for vital homeostasis, differentiation, development, reproduction, and/or behavior. It is important consideration for assessing the adverse effects of EDCs to have an understanding of normal endocrine systems, subsequently, dose, duration of exposure, age, sex, situation, and frequency are estimated.
  • Nariaki Fujimoto
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 65
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Estrogenic chemicals, a majority of endocrine distuptors, could cause two types of effects on the anterior pituitary gland. The one is the induction of the pituitary tumor (prolactinoma); the other is stimulating the production and release of pituitary hormones, prolactin and TSH, in the gland. Since the minimum dose of estrogen for inducing pituitary tumors is very high, more than the physiological level, it is unlikely that any weak estrogenic chemicals are directly carcinogenic in the pituitary gland. However, once the tumors have developed, their growth response would be strongly sensitive to estrogen and endocrine disruptors may effect on it. On the other hand, they could easily influence the production of prolactin and TSH and may cause the development of mammary and thyroid tumors.
  • Masao Hirose, Akiyoshi Nishikawa, Makoto Shibutani, Kunitoshi Mitsumor ...
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 71
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Thyroid cell proliferation caused by environmental compounds is well known to be associated promotion of carcinogenesis. For example, kojic acid, a secondary fungal metabolite, induces cell proliferation in rat thyroid follicular epithelium, and promotes thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). This was due to negative feedback through the pituitary-thyroid axis caused by inhibition of iodide uptake and iodine organification. Subcutaneous cholesterol pellets containing 17β-estradiol 3-benzoate also enhance rat thyroid carcinogenesis in ovariectomized female rats initiated with DHPN, although this was not the case with weak endocrine disrupting chemicals such as methoxychlor, atrazine and bisphenol A, which rather caused inhibition, possibly due to decrease in body weight gain. A high soybean diet enhances thyroid cell proliferation with increase in serum TSH level in synergism with a low iodine diet, presumably soybean diet primarily stimulate serum TSH release from the pituitary specifically under iodine deficiency conditions.
  • Yasuyoshi Okuno, Kaori Miyata
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 79
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    A 5-day Hershberger assay, a 20-day pubertal male assay, a one-month oral administration study and a reproductive toxicity study were carried out using an antiandrogenic chemical, flutamide (FL). The effects of FL were as follows: weight decrease in male reproductive organs such as the prostate and seminal vesicles were observed at ≥0.6 mg/kg/day as the most sensitive parameter in the Hershberger assay and the one-month oral administration study. Reduction in number of spermatogenic cells was found at ≥0.6 mg/kg/day as the most sensitive parameter in the 20-day pubertal male assay. A decrease in the anogenital distance was observed at ≥2.5 mg/kg/day as the most sensitive parameter in the reproductive toxicity study. These effects were compared with the reported results of one-month oral administration study of an estrogenic chemical, ethinylestradiol (EE), and an androgenic chemical, methyltestosterone (MT). Differences in the results were as follows: serum hormone levels of LH and testosterone were increased by the FL-treatment, but decreased with EE despite testicular atrophy in all cases. While EE and MT produced atrophic changes in Leydig cells, FL induced their hyperplasia. Thus, different results were obtained regarding serum hormone levels and histopathological changes in Leydig cells with the endocrine disruptor. Attention should be concentrated on these two parameters to clarify and characterize the mechanisms of action of so called endocrine disruptors.
  • Midori Yoshida, Shin-ichi Katsuda, Akihiko Maekawa
    原稿種別: None
    専門分野: None
    2001 年 14 巻 1 号 p. 83
    発行日: 2001年
    公開日: 2001/06/01
    ジャーナル フリー
    Effects of estrogenic endocrine disrupting chemicals (EDCs) on the female reproductive tract, in addition to uterine carcinogenesis, in rats exposed at adulthood or perinatal period were investigated. In adult normal cycling and ovariectomized (OVX) rats, high dose exposure to p-tert octylphenol (OP) directly exerted estrogenic activity on the uterus and vagina, the minimum effective level being lower in OVX rats than normal cycling ones. Serum concentrations of OP were detected at similar levels in both normal cycling and OVX rats and the effects increased with a dose- and time-dependent manner, indicating that the OVX rats are more sensitive for detection of estrogenic activity of chemicals. Neonatal exposure to high dose OP showed irreversible effects on the female reproductive tract of rats. Various effects such as persistent estrus, atrophic and polycystic ovary and luminal-epithelial hyperplasia were considered to be due to disruption of the hypothalamus-pituitary-gonadal control system, whereas the inhibition of uterine gland-genesis might be direct estrogenic action of OP. Our data of perinatal or adulthood exposure to high dose estrogenic EDCs with or without carcinogen using Donryu rats provided that the EDCs promoted uterine carcinogenesis in rats.
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