Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells.
The interaction between a chemical and a cell may strongly depend on whether this cell is normal or pathological. Side effects of anticancer drugs may sometimes overcome their benefit action, so it is important to investigate their effect in both the target and normal cells. Capecitabine (Xeloda, CAP), a prodrug of 5-fluorouracil, is mainly used in colon cancer, but little is known about its action in head and neck cancer. We compared the cyto- and genotoxicity of CAP in head and neck HTB-43 cells and normal human lymphocytes by comet assay and flow cytometry. CAP at concentration up to 50 μM significantly decreased the viability of the cancer cells, whereas it did not affect normal lymphocytes. The drug did not interact with isolated plasmid DNA, but it damaged DNA in both cancer and normal cells. However, the extent of the damage in the former was much higher than in the latter. CAP induced apoptosis in the cancer cells, but not in normal lymphocytes. Pre-treatment of the cells with the nitrone spin traps α-(4-pyridil-1-oxide)-N-tert-butylnitrone and N-tert-butyl-α-phenylnitrone decreased the extent of CAP induced DNA damage, suggesting that free radicals may be involved in the formation of DNA lesions induced by CAP. The drug evoked an increase in the G0/G1 cell population accompanied by a decrease in the S cell population. CAP may evoke a pronounced cyto- and genotoxic effects in head and neck cancer cells, whereas it may or may not induce such effects in normal cells to far lesser extent.
Department of Gastroenterology and Internal Medicine, Medical University of Lodz, 90-647, Lodz, Poland.
Maria
M
Wisniewska-Jarosinska
Tomasz
T
Sliwinski
Jacek
J
Kasznicki
Dariusz
D
Kaczmarczyk
Renata
R
Krupa
Karolina
K
Bloch
Jozef
J
Drzewoski
Jan
J
Chojnacki
Janusz
J
Blasiak
Alina
A
Morawiec-Sztandera
D000069287:Capecitabine; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D018307:Neoplasms, Squamous Cell / Q000473:pathology; D010957:Plasmids / Q000378:metabolism; D013113:Spin Labels; D013997:Time Factors
D004270:DNA, Circular; D009153:Mutagens; D013113:Spin Labels; D003841:Deoxycytidine; D000069287:Capecitabine; D045643:DNA Repair Enzymes; D005472:Fluorouracil