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Leukocytosis in Mice Following Therapy with a Novel Antitumor Agent, RA-700
Authors:Taketoshi Kato  Yasuko Suzumura  Fen-Zhi Liu  Hiroo Tateno  Toshiaki Ogiu  Kazuo Ota
Affiliation:Laboratory of Chemotherapy, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464, Japan;Laboratory of Biochemistry, Cancer Research Institute, Harbin Medical College, Nangang District, Harbin, China;Laboratory of Pathology, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464, Japan;Laboratory of Ultrastructure Research, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464, Japan;Department of Internal Medicine, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464, Japan
Abstract:Nine daily intravenous (iv) injections of RA-700 (an antitumor cyclic hexapeptide) at doses of 2 to 6 mgAg/day caused increases of WBC counts at 4–6 days after treatment in normal C57BL/6 × DBA/ 2 (BDF1) mice. The percentages of neutrophils and lymphocytes were modified. There was a decrease of colony-forming units in culture (CFUc) in bone marrow to 40% of the control value on day 1 but CFUc rapidly returned to normal values on day 3. The colony-forming units in spleen (CFUs): in bone marrow decreased during treatment. On the other hand, CFUc and CFUs in spleen were increased from the initiation of treatment to the time prior to the increase of WBC count. Spleen weight increased after treatment, and histologically, increases of immature and also mature granulocytes and megakaryocytes were observed. However, RA-700 did not stimulate the progress of hematoprogenitors in vitro. The results indicated that RA-700 stimulates the progress of hematoprogenitors in the spleen, but this effect is probably indirect.
Keywords:Leukocytosis    RA-700    Antitumor agent    Cyclic hexapeptide
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