Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells.
Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells.
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DOI：
10.1007/s11033-010-0482-7
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发表时间：
2011-08
影响因子：
2.8
通讯作者：
Morawiec-Sztandera A
中科院分区：
文献类型：
--
作者：
Wisniewska-Jarosinska M;Sliwinski T;Kasznicki J;Kaczmarczyk D;Krupa R;Bloch K;Drzewoski J;Chojnacki J;Blasiak J;Morawiec-Sztandera A
化学物质和细胞之间的相互作用可能在很大程度上取决于该细胞是正常的还是病态的。抗癌药物的副作用有时可能会超过其有益作用，因此研究其在靶细胞和正常细胞中的作用是很重要的。卡培他滨（希罗达，CAP），5-氟尿嘧啶的前药，主要用于结肠癌，但很少有人知道它在头颈癌的作用。采用彗星试验和流式细胞术比较CAP对头颈部HTB-43细胞和正常人淋巴细胞的细胞毒性和遗传毒性。CAP在浓度高达50 μM时显著降低癌细胞的活力，而它不影响正常淋巴细胞。这种药物不与分离的质粒DNA相互作用，但它会破坏癌细胞和正常细胞中的DNA。然而，前者的损害程度远高于后者。CAP诱导癌细胞凋亡，但不诱导正常淋巴细胞凋亡。用硝酮自旋捕获剂α-（4-吡啶-1-氧化物）-N-叔丁基硝酮和N-叔丁基-α-苯基硝酮预处理细胞可减轻CAP对DNA的损伤，提示自由基可能参与了CAP对DNA损伤的形成。该药物引起G 0/G1细胞群的增加，伴随着S细胞群的减少。CAP在头颈癌细胞中可能引起明显的细胞毒性和遗传毒性作用，而在正常细胞中可能或可能不引起这种作用，但程度要小得多。
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.
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影响因子：
8.4
作者：
Miwa, M;Ura, M;Ishitsuka, H
通讯作者：
Ishitsuka, H
影响因子：
50.5
作者：
Díaz-Rubio, E;Evans, TRJ;Baselga, J
通讯作者：
Baselga, J
DOI：
10.1016/s1383-5718(02)00289-9
发表时间：
2003-02-05
影响因子：
1.9
作者：
Blasiak, J;Gloc, E;Pertynski, T
通讯作者：
Pertynski, T
影响因子：
3.1
作者：
Rustum, YM
通讯作者：
Rustum, YM
影响因子：
9.7
作者：
Ooyama, Akio;Oka, Toshinori;Fukushima, Masakazu
通讯作者：
Fukushima, Masakazu