engleski

Application of the alkaline comet assay and sister chromatid exchange analysis for monitoring DNA damage in white blood cells of breast cancer patients under cytostatic therapy

The alkaline comet assay and sister chromatide exchange analysis were employed to evaluate the genotoxic effects of cytostatic therapy in 20 female patients with breats cancer. During study, all patients were given adjuvant chemotherapy according to CMF (Cyclophosphamide, methotrexate, 5-fluorouracyl), FAC ( 5-fluorouracyl, adriamycin, cyclophosphamide) and AC(adriamycin, cyclophosphamide) protocols. To quantify the levels of primary DNA damage in white blood cells before and afterchemotherapy two comet parameters wer studied ; tail length and tail moment. Pre- and post-therapy freuquencies od sister chromatid exchanges and mitotic activity have been evaluated in PHA-stimulated lymphocytes. The results obtained using both methods indicate considerable interindividual variations between the levels of DNA damage in white blood cells of breast cancer patients before chemotherapy. After intraveous administration of antineoplastic drugs in all patients significantly increased levels of DNA damage compared to rheir pre-treat, ent values were observed. Following chemotherapy the lymphocyte mitotic activity in vitro was also significantly disturbed, with marked delays and retardations in cell cycle progression. With regard to the results obtained it can be concluded that the patients with breast cancer show increase levels of DNA damage and chromosomal instability which is strongly modulated by chemotherapy protocols employed. Alkaline comet assay and sister chromatid exchange analysis were powerful biomarkers that enable sensitive detection of critical DNA lesions produced in white blood cells of breast cancer patients after administration of standard chemotherapy protocols. Beside both test could be used in biomonitoring of cancer patients in remission, they might be also helpful in pre-clinical evaluation of particular chemotherapy protocols before starting with cancer therapy.

breast cancer patient; comet assay; sister chromatid exchange analysis; white blood cells

nije evidentirano