Lack of Mutagenicity of SMD-502, a New Vitamin D3 Analog for Topical Application, in Skin and Liver of gpt delta Transgenic Mice and in GDL1 Cells

Genes and Environment

Koji Yamaguchi¹  Akira Kawase¹  Akira Takeiri¹  Asako Harada¹  Masayuki Mishima¹  Tetsuya Mitsui¹  Akifumi Shioda¹  Kenji Tanaka¹  Mariko Yano¹ 

[1] Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.

关键词: vitamin D3;    gpt delta mouse;    skin;    mutagenicity;   

DOI  :  10.3123/jemsge.34.107

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(14)SMD-502, a new vitamin D3 (VD3) analog, is an antipsoriatic drug candidate. The compound exhibited fewer side effects than known VD3 analogs in animal models, probably because the compound is rapidly converted into pharmacologically inactive form after permeating into systemic circulation from the application site on skin. This feature of the compound makes it difficult to assess genotoxic risk in vivo with the standard approach of bone marrow or peripheral blood micronucleus assays in rodents because of the low blood concentration level. To evaluate in vivo mutagenicity of the compound in the present study, mutant frequency (MF) in skin and liver of gpt delta transgenic mice was examined with percutaneous administration of SMD-502 for 28 days. In tissues collected 7 days after the end of administration, no significant increase in the MF was observed in either skin or liver. Additionally, when the compound was tested in a GDL1 cell line established from gpt delta mice, GDL1 cells exhibited no significant increase in MFs even under conditions in which they would be exposed to a much higher concentration of the compound than in the in vivo study. The results in this study further supported the consideration that SMD-502 has no mutagenic activity.

【 授权许可】

Unknown