Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients.
Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy or radiotherapy. However, clinicians should advise their patients against using antioxidant dietary supplements during chemotherapy. Irinotecan (CPT-11) is a common chemotherapeutic agent, but it causes side effects, including genotoxicity with damages the DNA of blood cells. The aim of this work was to evaluate the modulating effect of A, C and E vitamins on genotoxic activity of irinotecan (CPT-11) and to analyse the efficacy of DNA repair in lymphocytes of both patients with diagnosed colorectal carcinoma and healthy individuals in vitro. In healthy donors' cells CPT-11 did not exert a strong, genotoxic effect, both in the presence of vitamins and without them. In turn, a statistically significant increase of DNA migration in the comet tails was noted in patients' lymphocytes. The presence of vitamins A, C and E in incubation solutions acted synergistically, increasing the level of DNA lesions in cells caused by the exposure of the material on tested irinotecan concentrations. Analysis of the efficacy of DNA repair, performed after 2h of postincubation, showed the decrease of DNA percentage in comet tails in all experimental samples.
Laboratory of Cytogenetics, Department of General Genetics, Molecular Biology and Plant Biotechnology, University of Lodz, Poland. renkon@biol.uni.lodz.pl
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Grzegorczyk
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009153:Mutagens; D014801:Vitamin A / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D014801:Vitamin A; D014810:Vitamin E; D000077146:Irinotecan; D001205:Ascorbic Acid; D002166:Camptothecin