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Effects of Single Cyclophosphamide Doses on the Kinetics of Thoracic Duct Lymph and Blood Leukocytes in Calves¹

Institute for Clinical and Experimental Cancer Research [H. P. W., A. G.] and Institute of Pathology, University of Berne, Berne, Switzerland [H. C.], and Medical Research Center, Brookhaven National Laboratory, Upton, Long Island, New York 11973 [A. D. C., E. P. C., D. D. J., J. A. L.]

After 5 or 20 mg cyclophosphamide per kg body weight, given once i.v., the output in thoracic duct lymph of small and large lymphoid cells, cells incorporating [³H]thymidine in vitro, mitotic cells, pyknotic cells, and/or the number of lymphocytes and neutrophils in peripheral blood were measured in six calves. The median grain count of labeled cells and the DNA content of pyknotic nuclei were determined. After both doses there was an exponential decrease and subsequent recovery of the median grain count. The larger dose caused a temporary cessation of lymphoid cell division, reduced the output of nondividing small lymphoid cells, and probably impaired proliferation of neutrophil precursors. The results suggest that increased cell production during recovery was due to changes in the growth fraction and that feedback mechanisms acting on G₀-G₁ cells controlled the proliferation of lymphoid cells.

¹ Supported in part by Research Grants 3.583.71, 3.8470.72, and 3.3370.74 of the Swiss National Foundation for Scientific Research, the Swiss Cancer League, and the United States Energy Research and Development Administration. The research described in this report involved animals maintained in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care.

² To whom requests for reprints should be sent, at Institute for Clinical and Experimental Cancer Research, Tiefenau-Hospital, 3004 Berne, Switzerland.

Received 1/29/76. Accepted 4/12/76.