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Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-positive Chronic Myeloid Leukemia and Normal Bone Marrow¹

Innere Universitäts- und Poliklinik (Tumorforschung), Westdeutsches Tumorzentrum, Hufelandstrasse 55, 4300 Essen 1, Federal Republic of Germany

Cytogenetic effects of busulfan in vitro were studied in normal bone marrow (nine cases) and Philadelphia chromosome (Ph)-positive cells (10 cases) of patients with chronic myeloid leukemia. The frequency of chromosome aberrations and sister chromatid exchange (SCE) increased dose dependently. While there were no significant differences between normal and leukemic cells with regard to the induction of chromosome aberrations, the frequency of SCE was significantly lower in Ph-positive cells than in normal bone marrow. This difference was not only apparent on the basis of the SCE frequency per cell, but also when the SCE frequency was correlated to the relative chromosome length as shown by the SCE rate per chromosome group. Longitudinal studies of three patients who received long term busulfan treatment did not show a significant change in the frequency of induced SCE. It can be suggested that the lower frequency of induced SCE in Ph-positive cells reveals less sensitivity of the leukemic cells to DNA damage by busulfan. Our data provide evidence for the inability of busulfan treatment to eradicate or even reduce Ph-positive cells in chronic myeloid leukemia. Evaluation of cell proliferation by sister chromatid differentiation shows longer cell cycle times for the Ph-positive cells. Busulfan affected the cell cycle duration of leukemia and normal cells very little.

¹ Supported by the Deutsche Forschungsgemeinschaft (SFB 102, A7).

² To whom requests for reprints should be addressed.

Received 12/30/87. Revised 3/15/88. Accepted 3/18/88.