DNA strand breaks and DNA cross-links in peripheral mononuclear blood cells of ovarian cancer patients during chemotherapy with cyclophosphamide/carboplatin.
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.
Hengstler
J G
JG
Institute of Toxicology, University of Mainz, Germany.
Fuchs
J
J
Oesch
F
F
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage; D006224:Cricetinae; D003520:Cyclophosphamide / Q000008:administration & dosage; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000097:blood / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*
D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D003520:Cyclophosphamide; D016190:Carboplatin