Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Volume 15 , Issue 4
Showing 1-5 articles out of 5 articles from the selected issue
Originals
  • Hideki Wanibuchi, Keiichirou Morimura, Wei Min, Toshio Ichihara, Yoshi ...
    Type: Original
    Subject area: None
    2002 Volume 15 Issue 4 Pages 197-201
    Published: 2002
    Released: December 28, 2002
    JOURNALS FREE ACCESS
    The purpose of this study was to clarify whether the anti-angiogenesis drug TNP-470 may exert inhibitory effects on rat urinary bladder papillomatosis. A total of 46, six-week-old, male F344/DuCrj rats were used. In groups 1 and 2, 20 male F344/DuCrj rats each underwent intravesical instillation of 5 beads (1.5 mm diameter) via the abdomen to cause mechanical irritation. Group 3 was included as a control group without beads. Rats in group 1 were then treated with subcutaneous (s.c.) injections of TNP-470 at the dose of 30 mg/kg body wt, 3 times a week for 4 weeks. The vehicle alone was injected s.c. for groups 2 and 3. Subgroups of animals (10 rats each in groups 1 and 2, and 3 in group 3) were killed at weeks 2 and 4 after the beginning of the experiment. Urinary bladder weights of rats treated with intravesical instillation of beads (groups 1 and 2) were significantly increased compared with normal control rats (group 3). There was no difference between urinary bladder weights and calculi weights of groups 1 and 2 at 4 weeks. Histologically, the urinary bladder epithelium of rats suffering mechanical irritation due to the beads (groups 1 and 2) was significantly hyperplastic, demonstrating papillomatosis. There were no significant differences in the degrees or extents of epithelial lesions between groups 1 and 2. Furthermore, elevation of ODC and SAT activities, biomarkers of cell proliferation, in the epithelium was similar in both groups. TNP-470 thus did not inhibit epithelial proliferation in the urinary bladder in this experiment.
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  • Hiroshi Onodera, Toshio Imai, Hisayoshi Takagi, Toru Tamura, Makoto Ue ...
    Type: Original
    Subject area: None
    2002 Volume 15 Issue 4 Pages 203-207
    Published: 2002
    Released: December 28, 2002
    JOURNALS FREE ACCESS
    To cast light on the mechanisms of rapid induction of endometrial stromal sarcomas in p53-deficient CBA mice [p53 (+/-) mice] treated with ethinylestradiol (EE) after a single injection of N-ethyl-N-nitrosurea (ENU), p53 (+/-) and CBA/JNCrj mice [CBA mice] were given diet containing 2.5 ppm EE for 26 and 50 weeks, respectively, after ENU-initiation, and the types of uterine tumors induced were compared. Endometrial adenocarcinomas and stromal sarcomas were induced in 7% and 73%, respectively, of the p53 (+/-) mice given ENU followed by EE. In contrast, the CBA mice demonstrated incidences of adenocarcinomas and sarcomas of 100% and 25%, respectively. These results suggest that the uterine stromal cell is a major target cell of ENU-initiation in p53 (+/-) mice with a role for the tumor suppressor in governing its response to genetic damage due to ENU. The uterine epithelial cell is another target cell but subsequent long-term EE treatment appears prerequisite for the development of adenocarcinomas. While endometrial stromal sarcomas in p53 (+/-) mice were negative for p21 immunohistochemistry, their counterparts in CBA mice were focally positive at a high incidence, suggesting differences in the processes leading to the tumor development in the two cases.
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  • Norimitsu Shirai, Tetsuya Tsukamoto, Masami Yamamoto, Takeshi Iidaka, ...
    Type: Original
    Subject area: None
    2002 Volume 15 Issue 4 Pages 209-214
    Published: 2002
    Released: December 28, 2002
    JOURNALS FREE ACCESS
    Mutation of the p53 tumor suppressor gene is a common genetic alteration in human squamous cell carcinoma of the tongue. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we investigated the susceptibility of p53 nullizygous (-/-), heterozygous (+/-), and wild type (+/+) mice to methyl-n-amylnitrosamine (MNAN) induced squamous cell carcinoma (SCC) of the tongue. The p53 (+/-), and (+/+) mice were treated with 5 p.p.m. MNAN in drinking water for 8 weeks then held without further treatment for an additional 7 or 17 weeks, and killed at 15 or 25 experimental weeks. A separate group of the p53 (-/-) mice were given 5 p.p.m. MNAN for 8 weeks and were killed at 15 weeks. At 15 weeks, SCCs and papillomas were observed in 5/12 (41.7%) and 2/12 (16.7%) of p53 (-/-) mice, respectively, but not in p53 (+/-) and (+/+) mice. At 25 weeks, carcinomas in situ (CIS) were detected in 1/16 (6.3%) of p53 (+/-) and 1/13 (7.7%) of p53 (+/+) mice, and a papilloma was observed in the p53 (+/-) mouse which had CIS. PCR-single strand conformation polymorphism analysis of exons 5-8 of the p53 gene demonstrated a missense mutation in the CIS from p53 (+/+) mouse. These results suggest that a lack of p53 gene function predisposes the tongue to the development of SCCs in mice treated with MNAN, and show that p53 (-/-) mouse was a useful model for demonstrating carcinogenicity of MNAN to tongue.
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  • Junko Itoh, Yoko Kashida, Takao Watanabe, Kazuo Yasuhara, Tamotsu Taki ...
    Type: Original
    Subject area: None
    2002 Volume 15 Issue 4 Pages 215-220
    Published: 2002
    Released: December 28, 2002
    JOURNALS FREE ACCESS
    Glycerol has been reported to have a promoting effect in pulmonary tumorigenesis induced by 4-nitroquinoline-1-oxide (4NQO) in ddY mice, but not in mice pretreated with urethane (UR) or 3-methylcholanthrene (3MC). To investigate the modifying effects of glycerol on the development of lung tumors induced by UR or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), transgenic CB6F1 mice carrying the human proto-type c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) were given a single intraperitoneal injection of UR or NNK. One week after the treatment of the carcinogen, they were allowed to drink 5% solution of glycerol ad libitum for 26 weeks. In rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas, and carcinomas were induced in UR alone, UR + glycerol, NNK alone, and NNK + glycerol groups, but there were no significant differences in the incidences and multiplicity between UR alone and UR + glycerol groups or NNK alone and NNK + glycerol groups. In non-Tg mice, hyperplasias and adenomas were induced in UR alone, UR + glycerol, NNK alone, and NNK + glycerol groups, but no significant difference was observed between UR alone and UR + glycerol groups or NNK alone and NNK + glycerol groups. These results suggest that glycerol does not have a promoting effect in pulmonary carcinogenesis in rasH2 mice induced by urethane or NNK.
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Short communication
  • Yukiko Muto, Michio Suzuki, Yoshiro Tani, Kei-ichi Katayama, Kunio Doi
    Type: Short Communication
    Subject area: None
    2002 Volume 15 Issue 4 Pages 221-224
    Published: 2002
    Released: December 28, 2002
    JOURNALS FREE ACCESS
    In this study we investigated the effect of T-2 toxin (4 or 8 mg/kg/b.w.), a kind of trichothecene mycotoxins produced by the genus Fusalium, on the expression of connexin 32 (Cx32), a major protein of gap-junction, in mice. The area of total Cx32-positive spots on the immunostained section showed a tendency to be reduced from 6 to 36 hours after T-2 toxin inoculation (HAI), and it was significantly reduced at 36 HAI, irrespective of the dose of T-2 toxin. The value of Cx32 protein detected by Western blot analysis showed a tendency to be reduced from 3 to 48 HAI except at 6 HAI, and it was significantly reduced at 12 HAI, irrespective of the dose of T-2 toxin. Such reduction in Cx32 protein expression may be related to the depression of protein synthesis and induction of free radicals by T-2 toxin.
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