Progression process and safety assessment adaptation of endometrial lesions in ENU-induced 2-stage uterine carcinogenicity in a Tg-rasH2 mouse model

Journal of Toxicologic Pathology
Hiroyuki KurodaYuji Oishi

Abstract

Although acotiamide hydrochloride hydrate (acotiamide-HH) has not been reported to have genotoxic findings in any of the genotoxicity studies or treatment-related toxicological findings in reproductive and developmental studies, suspicious uterine tumorigenesis was observed in the results of a long-term rat carcinogenicity study. To clarify the uterine tumorigenesis of acotiamide-HH, we performed a 2-stage uterine carcinogenicity model in the transgenic rasH2 mouse initiated by N-Ethyl-N-nitrosourea (ENU). This model facilitated the short-term detection of uterine carcinogenic potential, and it appears to be a very useful testing method for assessing the safety of chemicals that may affect uterine tumorigenesis. However, there have not been many reports on this model, and accumulation of case studies using this model is recommended to support its usability. In this study, we performed this carcinogenesis model to not only confirm uterine tumorigenesis of acotiamide-HH but also to confirm the reliability of the model. The results of this study revealed that the endometrial adenocarcinoma found in the long-term rat carcinogenicity study possibly arose spontaneously. Also, we confirmed early induction of a uterine tumor as in prev...Continue Reading

References

Jan 1, 1990·Journal of Cancer Research and Clinical Oncology·T NagaokaA Maekawa
Oct 29, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·K MitsumoriM Hirose
Dec 6, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·James MacDonaldJan Willem van der Laan

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Citations

Mar 28, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Debabrata MahapatraRobert R Maronpot

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Methods Mentioned

BETA
transgenic
light microscopy

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