Regular Contributions
Modification of Mutagenic Activities
of Pro-Mutagens by Glyco-Ursodeoxycholic Acid in the Ames Assay
- MIYAKO
YOSHINARI,1 MASUE
IMAIZUMI,1,2 ATSUSHI
SATO,1 MASAYOSHI
MINEGISHI,4 KUNIHIRO
FUJII,1 HOSHIRO
SUZUKI,1 TOSHIHIKO
MIURA,3 TADAO
FUNATO,3 TOSHIAKI
SAITO,1 SHUJI
CHIKAOKA,1 TAKESHI
RIKIISHI,1 MASAHIRO
KIZAKI5 and KAZUIE
IINUMA1
- 1Department of Pediatrics,
2Department of Pediatric Hematology and Oncology,
3Department of Clinical and Laboratory Medicine, Tohoku
University School of Medicine, Sendai 980-8574,
4Department of Pediatric Oncology, Institute of
Development, Aging and Cancer, Tohoku University, Sendai 980-8575,
and 5Division of Hematology and Clinical Laboratories,
Keio University School of Medicine, Tokyo 160-8582
Granulocyte
colony-stimulating factor (G-CSF) is a cytokine that regulates the
proliferation, differentiation and survival of cells in the
granulocytic lineage. In this study, however, we found that G-CSF or
interleukin-6 (IL-6) induced UF-1, a human acute promyelocytic
leukemia cell line, into apoptosis that was confirmed by
morphological features and DNA fragmentation. This rare response is
demonstrated for the first time with human acute promyelocytic
leukemia cell line. The apoptosis induced by G-CSF or IL-6 was not
preceded by terminal differentiation characterized by morphological
maturation, capability to reduce nitroblue tetrazolium, or surface
CD11b expression. Interestingly, Western blot analysis revealed that
the stimulation of UF-1 with either G-CSF or IL-6 resulted in
excessive activation of both signal transducer and activator of
transcription 3a (Stat3a) and Stat3b. Furthermore, an additional 18 kDa
Bax-related protein was expressed by the stimulation of G-CSF or
IL-6, while Bcl-2 and Bcl-X proteins remained unchanged. These
findings suggest that UF-1 may be a valuable tool in investigating
the aberrant regulation of apoptosis, especially the Stat3
involvement in the mechanism of apoptosis induction.
Key words--- human APL cell line; apoptosis;
G-CSF; IL-6; Stat3
© 1999 Tohoku University Medical Press
Tohoku J. Exp. Med., 1999,
189, 71-82
Address for reprints: Masue Imaizumi, M.D., Department of
Pediatric Hematology and Oncology, Tohoku University School of
Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.
e-mail: mimaizumi@ped.med.tohoku.ac.jp
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