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Arrested by the treatment with busulfan gives more sensitivity in assessing the effect of injected materials. Received November 17, lYY5. Address all correspondence and requests for reprints to: H. L. Guenther, Ph.D., Department of Pathophysiology; University of Berne. Murtenstrasse 35, CH-3010 Berne, Switzerland. E-mail: guentier pphy be.ch * Portions of the present study were presented at the meeting of the American Society for Bone and Mineral Research, Kansas City, MO, September 1994. This work was supported by the Swiss National Science Foundation Grant 31.37623.93 ; and by a grant from Merck & Co., Inc., Whitehouse Station, NJ. Wash cut blow dry Dry cut Clipper cut with wash ; Beard trim Long hair with wash ; Usual Price 14.00 11.50 9.50 DaC driver's price 11.00 9.00 7.00. Fig. 2 shows the morphology in lymphoma cells. The neoplastic cells are larger than the lymphocytes in normal splenic white pulp. In tissue section, the nuclei of lymphoma cells are leptochromatic, while in smear preparations, the chromatin is delicate and finely distributed. The nucleoli generally are not evident; however, when seen, they are usually single and small to medium in size. The ratio of nucleus to cytoplasm is high, and the cytoplasm is basophilic and agranular. All mice with lymphomatous spleens had enlarged thymus and lymph nodes, which histologically were diffusely invaded by neoplastic cells resulting in effacement of normal architec ture. The liver and kidney were found to be involved in some lymphomatous mice. The liver contained a diffuse infiltration of neoplastic cells, that was most marked in the portal areas, and less prominent in the sinuses of the hepatic lobules. In the kidney, the interstitial tissue was diffusely infiltrated by neo plastic cells. Table 4 shows the results of cell surface marker determina tions on lymphomatous and control mice. In the mice with lymphomas, 87 to 100% of the lymphocytes in the blood, spleen, and thymus had cell surface markers, indicative of Tcell lineage. T- and B-cell markers done on peripheral blood of treated, nonlymphomatous mice revealed markers similar to those of control mice. Transplantation of spleen cell suspensions from 8 of 8 mice with lymphoma resulted in clinically evident lymphomas in 100% of the recipients within 3 weeks when injected with 106 cells and within 4 weeks when injected with 10s cells. All mice that received 106 cells were dead within 5 weeks, and all mice that received 105 cells were dead within 7 weeks. DISCUSSION The studies reported in this paper were undertaken initially to determine whether in mice chloramphenicol further influ ences hematopoiesis already altered by busulfan. Serendipitously, we observed that mice treated with both chloramphen icol and busulfan developed lymphomas earlier and more fre quently than did those treated with either agent alone. No lymphomas were detected in control CAFi mice, and this hybrid strain is not known to develop any tumor in particularly high incidence. 3480.

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Counts, testis volume measurements, and hematological parameters. For the purpose of histological evaluation and isolation of testicular cells, testis tissue was recovered by biopsy or hemicastration, before and after busulfan treatment Fig. 1A & 1E ; . small piece of each hemicastrated testis was used for morphological analyses and the remainder was used to generate a single cell suspension by two-step enzymatic digestion see below, Fig. 1A ; . Busulfan Treatment. Following initial testis tissue collection hemicastration or biopsy ; , animals were treated with the chemotherapeutic agent busulfan Busulfex IV; PDL BioPharma, Fremont, CA ; , at doses of 4, 8, and 12 mg kg 2 animals per group; Fig. 1C ; . Busulfex was diluted in physiological saline and administered at 1 mg ml in a single bolus infused over 5 minutes. Semen collection and analysis. Semen samples were collected from experimental and control animals at weekly intervals Fig. 1D ; , as described 18 ; . Total sperm count per ejaculate was determined by hemocytometer. Testis volume measurements. At weekly intervals, calipers were used to measure the longest diameter height ; and shortest diameter width ; of each testis through the scrotum of each experimental and control animal Fig. 1D ; . Testis volume was estimated using the equation for the volume of a prolate spheroid [GRAPHIC] ; . For animals with both testes, testis volumes were averaged. Blood collection and analysis. Blood was collected at weekly intervals and processed for complete blood count CBC; Antech Diagnostics, Lake Success, NY ; to measure hematopoietic parameters and determine the general health status of experimental animals Fig. 1D and byetta.

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