Chemotherapy-induced chromosomal damage in peripheral blood lymphocytes of cancer patients supplemented with antioxidants or placebo.
A total of 27 patients with various types of cancer were treated with cisplatin-based combination chemotherapy. Out of these, 13 patients were randomized to receive supplementation treatment with a beverage containing the antioxidants vitamins C and E, plus selenium, during chemotherapy. The antioxidant mixture was administered to investigate whether it could reduce the potential genotoxic and nephrotoxic effect of the applied chemotherapy. A placebo group of 14 cancer patients received a beverage without selenium or antioxidants. Micronuclei (MN) in cytochalasin B-blocked binucleate (BN) peripheral blood lymphocytes (PBLs) and hypoxanthine phosphoribosyl transferase (HPRT) mutants in PBLs were studied before, during and after chemotherapy as a measure for chemotherapy-induced genotoxic effects. Before chemotherapy, patients mean frequencies of MN and HPRT mutants did not differ from those in a group of 10 healthy subjects. The mean frequency of MN in patients increased significantly after one cycle of chemotherapy (P=0.002). This frequency was still elevated at 2 months after the completion of chemotherapy (not significantly). There was no significant difference in micronuclei frequency (MNF) between the antioxidant and placebo group of patients. Chemotherapy-induced frequencies of MN after three cycles of chemotherapy correlated significantly with the cumulative dose of cisplatin (r=0.58, P=0.012) and the cisplatin-mediated loss of renal function (r=0.53, P=0.03). No consistent change in HPRT mutant frequency following chemotherapy was observed in the placebo and antioxidant group of patients. In conclusion, cisplatin-combination chemotherapy resulted in a cisplatin dose-related increase of the frequency of chromosomal damage. Supplementation with antioxidants did not prevent or reduce this effect.
Elsendoorn
T J
TJ
Department of Clinical Oncology, Leiden University Medical Centre, Leiden, The Netherlands.
Weijl
N I
NI
Mithoe
S
S
Zwinderman
A H
AH
Van Dam
F
F
De Zwart
F A
FA
Tates
A D
AD
Osanto
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D002869:Chromosome Aberrations / Q000139:chemically induced*; D025063:Chromosome Disorders; D002875:Chromosomes / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D019587:Dietary Supplements; D005260:Female; D006309:Hearing / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007668:Kidney / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000188:drug therapy*; D012643:Selenium / Q000008:administration & dosage / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood
D000975:Antioxidants; D014810:Vitamin E; D007041:Hypoxanthine Phosphoribosyltransferase; D012643:Selenium; D001205:Ascorbic Acid; D002945:Cisplatin