Carcinogenesis Advance Access published online on April 14, 2005
Carcinogenesis, doi:10.1093/carcin/bgi095
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1 Division of Microbiology and Genetics, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
* To whom correspondence should be addressed. Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I). The nuclear transcription factor, NF-
Received December 28, 2004
Revised March 14, 2005
Accepted April 10, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
In vivo antitumor activity of the NF-
B inhibitor dehydroxymethylepoxyquinomicin in a mouse model of adult T-cell leukemia
2 Department of Hematology, Faculty of Medicine, Kitasato University, 1-15-1 Sagamihara, 228-8555, Japan
3 Department of Pathology (I), Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
4 Department of Computer and Media Science, Faculty of Engineering, Yamanashi University, 4-3-11 Takeda, Kofu, Japan
5 Division of Pathology, Department of Cancer Research, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
6 Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo 208-0011, Japan
7 Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan
Takeo Ohsugi, E-mail: ohsugi{at}gpo.kumamoto-u.ac.jp
Abstract 
B, is induced by HTLV-I and is central to the ensuing neoplasia. To examine the effect of a novel NF-B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on ATL in vivo, we developed an improved severe combined immunodeficiency (SCID) mouse model for ATL. Five-week-old SCID mice in which natural killer (NK) cell activity had been eliminated were inoculated intraperitoneally with the HTLV-I-infected cell lines, TL-Om1, MT-1, MT-2 and HUT-102. No engraftment of TL-Om1 cells and little tumorigenesis of MT-1 cells were detected 40 days after injection. In contrast, inoculation of mice with MT-2 and HUT-102 cells elicited high mortality, 100% frequency of gross tumor formation, and tumor cell infiltration of various organs, all of which were reduced by co-administration of DHMEQ during the inoculation. Moreover, tumors from mice treated with DHMEQ had a high frequency of apoptosis. These results suggest that DHMEQ induces apoptosis in HTLV-I-transformed cells in vivo, resulting in inhibition of tumor formation and organ infiltration, thereby enhancing survival.
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