DNA strand breaks and
DNA cross-links were detected in peripheral mononuclear blood cells of 15 ovarian
carcinoma patients by alkaline filter elution. These patients received
therapy with 600 mg/m2 of
cyclophosphamide and 350 mg/m2 of
carboplatin. Blood samples were taken a day before and 16 to 18 h after a
therapy cycle. The patients showed an increased elution rate of 37% compared with that of healthy controls before the current cycle of
chemotherapy, probably due to treatment in a previous cycle of
therapy. The difference was statistically significant (P < 0.02; U test). At the end of the actual cycle of
therapy an average acceleration of the elution rate of 157% was found compared with that of controls (P < 0.01; U test). Compared with the rate before the cycle of
therapy, the mean elution rate
after treatment was accelerated by 89% (P < 0.01; Wilcoxon test). The amount of
DNA-
protein cross-links was also increased after
drug application. The individual patients showed different responses after
drug intake. While some patients showed hardly any alteration in the elution rate, others showed an acceleration of up to 400%. Monitoring the course of disease in six of these patients indicated that a strong acceleration in the elution rate after
drug application is possibly linked to the success of the chosen
cancer treatment as measured by a decrease in the
tumor marker CA12-5 to the normal level. In another investigation the group of patients who had received non-
alkylating antineoplastic agents showed no increase in
DNA strand breaks compared with untreated controls. Thus, monitoring
DNA single-strand breaks in the peripheral mononuclear blood cells of patients can help to evaluate the efficiencies of the
cancer treatment as a composite of individual differences in resorption, metabolic activation and detoxification, and possibly some constitutional aspects of drug resistance to
cyclophosphamide/
cisplatin and probably to several other
alkylating antineoplastic drugs. This may help in choosing an effective
drug and in adjusting the doses of these drugs individually in the
chemotherapy of
cancer.