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Induction, Accumulation, and Persistence of Sister Chromatid Exchanges in Women with Breast Cancer Receiving Cyclophosphamide, Adriamycin, and 5-Fluorouracil Chemotherapy¹

Lawrence Livermore National Laboratory, Biomedical Sciences Division, University of California, Livermore, California 94551 [J. D. T., A. J. W., L. K. A., M. L. C., A. V. C.]; Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710 [G. V. B.]; and National Institute of Environmental Health Sciences, Epidemiology Branch, Biometry and Risk Assessment Program, Research Triangle Park, North Carolina 27709 [R. B. E.]

The induction, accumulation, and persistence of sister chromatid exchanges (SCEs) and high SCE frequency cells (HFCs) was measured in peripheral blood lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted of i.v. infusion of cyclophosphamide, Adriamycin, and 5-fluorouracil, administered on day 1 of each of approximately six 21-day cycles. This treatment resulted in a highly significant induction of SCEs (1.8-fold, P < 0.0001) and HFCs (5-fold, P < 0.0001) measured in samples obtained 1 week after the first therapy. Accumulation of lesions leading to SCEs was measured by comparing samples surrounding the first and last rounds of therapy and was significant for both SCEs and HFCs in most comparisons. Persistence of lesions leading to SCEs was evaluated at multiple times until 9 months after completion of therapy, and both SCEs and HFCs remained significantly elevated throughout this time. Differences between donors were observed throughout the study, although they were not always consistent with time. Our results also indicate that the SCE frequency declines rapidly within a few weeks after treatment but that residual damage remains up to 9 months after the end of chemotherapy.

¹ This project was conducted under the auspices of the United States Department of Energy by the Lawrence Livermore National Laboratory under contract W-7405-ENG-48, with funding under interagency agreements with the National Institute of Environmental Health Sciences (1 YO1 ES 3 0114-00) and with the Environmental Protection Agency (DW89932671).

² To whom requests for reprints should be addressed, at Lawrence Livermore National Laboratory, Biomedical Sciences Division, P.O. Box 5507, L-452, University of California, Livermore, CA 94551.

³ Present address: Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park, NC 27711.

Received 2/26/90. Revised 4/27/90.