Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
11 巻, 2 号
選択された号の論文の10件中1~10を表示しています
Mini review
  • Akihiro Ito, Takahiko Gotoh, Nariaki Fujimoto
    原稿種別: Mini Review
    専門分野: None
    1998 年 11 巻 2 号 p. 79
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    Cancer is a genetic disease and numerous genetic changes have been disclosed in its developmental stages. Corresponding to those endogenous events, environmental factors including chemicals, oncogenic viruses, and radiation participate in the initiation, promotion, and progression stages. Furthermore, development of cancer is greatly influenced by nutritional factors such as from daily food consumption and the additives in these foods. Retinoids, vitamins, essence of tea, and vegetables are believed to be highly effective in chemoprevention of cancer. In this mini review, miso, a fermented soy product, and the purported active chemopreventative component of soybeans, isoflavones, were examined for their biological activity; 1) during recovery from radiation induced damage, and 2) as a possible chemopreventor of cancers. Thus far, promising results have been obtained for prevention of liver tumors in mice, breast tumors in rats, and intestinal tract tumors in rats. Since chemopreventors derived from natural foods are not cytotoxic, they need not be given to the recipients intermittently. Furthermore, we have found that a combination of tamoxifen with miso greatly reduced occurrence of mammary tumors in rats and therefore might be applicable to human cancers.
Originals
  • Akihito Shimoi, Chihaya Kakinuma, Chitose Kuwayama, Mitsutoshi Watanab ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 85
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    We scrutinized the spontaneous histological lesions in 161 wild-caught cynomolgus monkeys (89 males and 72 females, age unknown) and 166 laboratory-bred rhesus monkeys (78 males and 88 females, from 3 to 5 years old) used in toxicity studies conducted at our laboratory. Various spontaneous lesions were observed in most of their organs. In the wild-caught monkeys, infestant lesions such as parasitic abscess and sarcocystis were mainly observed. On the other hand, in the laboratory-bred animals, the infestant lesions were rarely observed ; but edema in the renal papilla with or without intracellular edema of the papillary epithelium and gastritis associated with atrophy of the epithelium were observed frequently. The papillary lesions in the laboratory-bred animals were similar to the early changes of papillary necrosis or hyperplasia induced occasionally by drugs. It is generally considered that less variable data in hematology and biochemistry are obtained in laboratory-bred monkeys because the incidence of infectious or infestant lesions in them is less is less than that in wild-caught animals ; however, the spontaneous minor lesions were still observed frequently in the laboratory-bred animals. Furthermore, some spontaneous lesions even show histological similarity to the early lesions induced by drugs. Therefore, it is important to know the histological character of spontaneous lesions as well as their incidence for the pursuit of accurate evaluation of drug-induced toxicities in monkeys.
  • Kohji Tanaka, Isao Igarashi, Yoshihiko Ohashi, Kazuo Yamashita, Munehi ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 95
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    It has been reported that glucose feeding drastically potentiates the toxicity of several hepatotoxicants in rats. Accordingly, it was speculated that the potentiation mechanism involves the suppression of hepatocellular regeneration, i.e., the tissue healing process following initial damage. In this study, we quantitatively examined the effect of glucose feeding on hepatocellular regeneration following a partial hepatectomy (PH). Rats received a 15% glucose supplementation through drinking water for 7 days and control animals were supplied with tap water ad libitum. Following the glucose or tap water feeding, rats were subjected to a two-thirds PH. Glucose or tap water feeding was continued throughout the liver regenerative phase. On days 0, 1, 2, 4, and 7, serum and liver biochemical examinations, and measurements of liver weights, and immunohistochemical examinations on terminated animals, were conducted. The results demonstrated that liver weight gain was suppressed and the number of mitotic hepatocytes, an indicator of cell regeneration, was reduced by glucose feeding. These results support the speculation of hepatotoxicity potentiation by glucose feeding. Furthermore, changes of serum glucose and triglyceride levels, and hepatic glycogen and triglyceride contents were also observed in glucose-fed rats, indicating changes in glucose and triglyceride metabolism in the liver. However, the relationship between these biochemical changes and the suppression of liver regeneration remains to be clarified.
  • Katsuhiko Ishida, Ryutaro Okuda, Hisashi Ikegami, Kyoko Ito, Nami Naga ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 101
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    Male rats with fructose-induced hypertriglyceridemia become resistant to hepatotoxicity and more susceptible to nephrotoxicity of acetaminophen (APAP) as compared with normal male rats. To determine whether changes in APAP toxicity by fructose-treatment were sex-dependent, male and female rats were fed standard diet (non-pretreated rats) or high fructose diet (fructose-pretreated rats) for 3 weeks and then given a single ip dose of APAP at 800 mg/kg. At 24 hours after APAP dosing, they were sacrificed and examined histopathologically. Non-pretreated males showed severe hepatic lesions characterized by centrilobular hepatocyte necrosis and slight renal lesions characterized by single cell necrosis in the proximal straight tubules, while females showed no hepatic lesions and milder renal lesions than males. APAP-induced hepatotoxicity was prevented and APAP-induced nephrotoxicity was potentiated in fructose-pretreated males. In contrast, no apparent changes on APAP-induced toxicity were seen in fructose-pretreated females. Castration partially prevented such enhancement of APAP-induced nephrotoxicity in fructose-pretreated males. Furthermore, castration and estradiol treatment had greater protective effect against the enhancement of APAP-induced nephrotoxicity in fructose-pretreated males as compared with castration alone. Ovariectomy potentiated the enhancement of APAP-induced nephrotoxicity in females. These results indicate that the changes in APAP-induced hepatorenal toxicity by fructose-pretreatment are sex-dependent.
  • Tetsuro Kurotaki, Hitoshi Onuma, Yasuko Arai, Kazunori Ike, Toshifumi ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 109
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    Dermonecrotic toxin (DNT) produced by Pasteurella multocida was purified by anion-exchange chromatography, gel filtration, and high-performance liquid chromatography. Pigs were given an intramuscular injection of P.multocida dermonecrotic toxin (Pm-DNA), which produced necrotic lesions of the liver. Liver sections were taken at intervals of 2, 12, and 24 hours after Pm-DNA injection. We examined the sections histopathologically, immunopathologically, and electron microscopically. The earliest alterations observed were loss of glycogen from hepatocytes, which became more severe during later intervals, vacuolation and single-cell necrosis of hepatocytes, as well as desquamation and fragmentation of the sinusoidal endothelium. The vacuoles subsequently increased in quantity and size with the passage of time and found to contain homogeneous fine material and/or fibrillar material. These materials were thought to be fibrin and blood serum. The vacuoles penetrated the cytoplasm of the hepatocytes. We considered that liver necrosis caused by Pm-DNT probably resulted from the principal effects of vascular injury, although the membrane of the hepatocytes was more or less damaged by the toxin.
  • Yoshiro Tani, Shinji Murata, Sachiko Kajiwara, Hatsue Mizuno, Junichir ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 119
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    A histopathological study was carried out on the liver of thioacetamide (TAA)-treated rats of Jcl: Wistar-TgN(ARGHGEN)1Nts strain (Mini rats), in which the expression of growth hormone (GH) gene is suppressed by the presence of antisense transgene, resulting in the reduction of plasma GH levels. Male Wistar (the parental strain of Mini rats) and Mini rats of 4-6 weeks of age were treated with 0.03% TAA in drinking water for up to 8 weeks. The survival rates of Wistar and Mini rats were 91% and 89%, respectively. Plasma alkaline phosphatase activity and total bilirubin concentration in TAA-treated Mini rats increased to a greater extent than those in TAA-treated Wistar rats. Histopathologically, the liver of TAA-treated Mini rats revealed proliferation of ‘atypical’ hepatocytes throughout the course of the experiment. In addition, fibrosis from the periportal area to the centrilobular region associated with oval cell proliferation was observed at 2 weeks. At 8 weeks, cirrhosis accompanied with proliferation of bile duct epithelial cell-like cells was evident. In the liver of Wistar rats, There were only atypical hepatocytes and slight fibrosis without cirrhotic features even at 8 weeks. These results demonstrate a great advantage in the use of Mini rats to produce liver cirrhosis within a short term and suggest some possible relationships between GH deficiency and experimental cirrhogenesis.
  • Hiroyuki Nambu, Katsuhiko Yoshizawa, Jihong Yang, Daigo Yamamoto, Airo ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 127
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    The morphologic response of the rat retina at different ages to the various doses of the alkylating agent N-methyl-N-nitrosourea (MNU) was examined. MNU at the dose of 35, 50, 75, 90, and/or 105 mg/kg was injected intraperitoneally (ip) to male and female Sprague-Dawley and Lewis rats at 0, 21, 50, and 150 days of age, and the retinas were examined 7 or 21 days after the treatment. In both strains of rats, regardless of gender, MNU evoked age-specific and dose-dependent retinal lesions. When ≥ 50 mg/kg MNU were administered at day 0, retinal dysplasia characterized by rosette formation was found in the outer neuroblastic/nuclear layer above the continuous lining single layer of pigment epithelial cells. The severity of the lesion was not dose-related. When > 90 mg/kg, > 50 mg/kg and ≥ 35 mg/kg MNU were administered at day 21, 50, and 150, respectively, retinal degeneration characterized by selective photoreceptor cell loss due to apoptosis with disorganized pigment epithelial cells was found in all rats. Thus, the sensitivity of photoreceptor cells in the development of retinal degeneration induced by MNU increased in parallel with aging.
  • Dong-ping Lu, Hiroyuki Nakayama, Junko Shinozuka, Koji Uetsuka, Ryuich ...
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 133
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    Pregnant Wistar rats were injected i.p. with 5-azacytidine (5AzC) at 11 day of gestation. Brain cell apoptosis determined morphologically or by TUNEL method was observed in the fetuses 3 hrs after injection. Eight to 100% of the fetuses were dead at 1 to7 day after injection. Injection with doses less than 5 mg/kg of 5AzC killed only a few fetuses, though neuronal apoptosis was detected in most of living fetuses. All fetuses were dead when their dams were injected with 5AzC at 9 or 10 day of gestation, whereas most of the fetuses were alive when injected after day 12. The present study revealed that 5AzC specifically induce neuronal apoptosis in rat fetuses at the stage of logarithmic growth.
  • Munehiro Teranishi, Yoshiro Tani, Sunao Manabe
    原稿種別: Original
    専門分野: None
    1998 年 11 巻 2 号 p. 137
    発行日: 1998年
    公開日: 2002/01/31
    ジャーナル フリー
    It has been reported that in Mini rats, rats of transgenic Jcl: Wistar-TgN (ARGHGEN) 1Nts strain, the expression of rat growth hormone (GH) gene was suppressed by the presence of an antisense transgene, resulting in lowered plasma GH levels compared with nontransgenic Wistar rats. GH is thought to have an important role in bone growth, but bone changes of Mini rats have not been reported. In the present study, we examined the femurs of both male Mini rats and male Wistar rats at different ages, i.e. 8 and 22 weeks of age, and compared them between both rat strains. As a result, Mini rats showed smaller sizes of the femur with low mineral densities histologically characterized by the metaphyseal and diaphyseal bone be a possible animal model for osteopenia.
Short Communication
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