ALKALINE SINGLE-CELL GEL-ELECTROPHORESIS AND HUMAN BIOMONITORING FOR GENOTOXICITY - A PILOT-STUDY ON BREAST-CANCER PATIENTS UNDERGOING CHEMOTHERAPY INCLUDING CYCLOPHOSPHAMIDE

Alkaline single-cell gel electrophoresis (the 'comet assay') was used to evaluate DNA damage in lymphocytes from 17 breast cancer patients b efore and 1-21 h after chemotherapy including cyclophosphamide (600-18 00 mg/m(2)). in order to control for the experimental variability over time, freshly isolated lymphocytes from female mice given physiologic al saline or cyclophosphamide (150 mg/kg b.wt.) were included as 'inte rnal standards' in each individual electrophoresis run. There was an u pward tendency of DNA damage in the mouse lymphocytes over the study p eriod, but cyclophosphamide was constantly found to induce significant damage at all time points investigated (1-48 h). Although patients gi ven up to Il prior cycles of chemotherapy showed the same basal level of DNA damage as the patients coming to the clinic for their first tre atment, the chemotherapy given at the time of the present blood sampli ng was associated with significant DNA damage in most samples. Conside rable interindividual variations were observed both before and after t he treatment. DNA single-strand breaks and alkali-labile sites in peri pheral lymphocytes as evaluated by the comet assay seem to be useful m olecular biomarkers for exposure to DNA damaging agents when monitorin g ongoing exposures, but less impressive when monitoring accumulated e xposures, at least in patients given high doses of cyclophosphamide an d other antineoplastic agents. (C) 1997 Elsevier Science B.V.