Induction, accumulation, and persistence of sister chromatid exchanges in women with breast cancer receiving cyclophosphamide, adriamycin, and 5-fluorouracil chemotherapy.
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 less than 0.0001) and HFCs (5-fold, P less than 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.
Tucker
J D
JD
Lawrence Livermore National Laboratory, Biomedical Sciences Division, University of California, Livermore 94551.
Wyrobek
A J
AJ
Ashworth
L K
LK
Christensen
M L
ML
Burton
G V
GV
Carrano
A V
AV
Everson
R B
RB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D012854:Sister Chromatid Exchange; D012907:Smoking; D013997:Time Factors
D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil