Botana L M, Arnaez E, Vieytes M R, Alfonso A, Bujan M J, Louzao M C, Cabado A
Departamentos de Farmacologia y Fisiologia, Facultad de Veterinaria, Universidad de Santiago, Lugo, Spain.
Cancer Chemother Pharmacol. 1992;29(6):495-8. doi: 10.1007/BF00684855.
We studied the histamine-releasing activity of several antineoplastic drugs on rat pleural and peritoneal mast cells. The drugs tested included the nitrogen mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine, vincristine and Vinorelbine, the epipodophyllotoxins etoposide and teniposide, and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil, vinblastine and vincristine failed to elicit histamine release on rat mast cells. All of the other drugs evoked histamine release in both the presence and the absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase induced a much lower release in the absence of this cation. The response elicited by cytarabine and etoposide was much higher in pleural than in peritoneal mast cells. These results indicate that some antineoplastic drugs may directly activate the release of histamine, which could contribute to some of their secondary effects.
我们研究了几种抗肿瘤药物对大鼠胸膜和腹膜肥大细胞的组胺释放活性。所测试的药物包括氮芥类的环磷酰胺和异环磷酰胺、亚硝基脲类的卡莫司汀、三嗪类的达卡巴嗪、叶酸类似物甲氨蝶呤、嘧啶类似物阿糖胞苷和氟尿嘧啶、长春花生物碱类的长春碱、长春新碱和长春瑞滨、表鬼臼毒素类的依托泊苷和替尼泊苷，以及酶L-天冬酰胺酶。甲氨蝶呤、卡莫司汀、氟尿嘧啶、长春碱和长春新碱未能在大鼠肥大细胞上引发组胺释放。所有其他药物在细胞外钙存在和不存在的情况下均能引起组胺释放，但异环磷酰胺、阿糖胞苷和天冬酰胺酶在没有这种阳离子的情况下诱导的释放要低得多。阿糖胞苷和依托泊苷在胸膜肥大细胞中引发的反应比在腹膜肥大细胞中高得多。这些结果表明，一些抗肿瘤药物可能直接激活组胺释放，这可能导致它们的一些副作用。
