title: DNA damage in peripheral blood lymphocytes in patients during combined chemotherapy for breast cancer.
abstract: Combined chemotherapy is used for the treatment of a number of malignancies such as breast cancer. The target of these antineoplastic agents is nuclear DNA, although it is not restricted to malignant cells. The aim of the present study was to assess DNA damage in peripheral blood lymphocytes (PBLs) of breast cancer patients subjected to combined adjuvant chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide, FEC), using a modified comet assay to detect DNA single-strand breaks (SSB) and double-strand breaks (DSB). Forty-one female patients with advanced breast cancer before and after chemotherapy and 60 healthy females participated in the study. Alkaline and neutral comet assays were performed in PBLs according to a standard protocol, and DNA tail moment was measured by a computer-based image analysis system. Breast cancer patients before treatment had higher increased background levels of SSB and DSB as compared to healthy women. During treatment, a significant increase in DNA damage was observed after the 2nd cycle, which persisted until the end of treatment. Eighty days after the end of treatment the percentage of PBLs with SSB and DSB remained elevated, but the magnitude of DNA damage (tail moment) returned to baseline levels. There was no correlation between PBL DNA damage and response to chemotherapy. DNA-SSB and DSB in PBLs are present in cancer patients before treatment and increase significantly after combined chemotherapy. No correlation with response to adjuvant chemotherapy was found. Biomonitoring DNA damage in PBLs of cancer patients could help prevent secondary effects and the potential risks of developing secondary cancers.
authors.affiliation: Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc # 330, Col. Doctores, 06725 México, D.F., Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sánchez-Suárez
authors.forename: Patricia
authors.initials: P
authors.lastname: Ostrosky-Wegman
authors.forename: Francisco
authors.initials: F
authors.lastname: Gallegos-Hernández
authors.forename: Rubicelia
authors.initials: R
authors.lastname: Peñarroja-Flores
authors.forename: Jorge
authors.initials: J
authors.lastname: Toledo-García
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bravo
authors.forename: Emilio Rojas
authors.initials: ER
authors.lastname: Del Castillo
authors.forename: Luis
authors.initials: L
authors.lastname: Benítez-Bribiesca
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000235:genetics*; D020552:Comet Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004249:DNA Damage; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008875:Middle Aged
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil