Nelson J A, Drake S
Cancer Res. 1984 Jun;44(6):2493-6.
Dipyridamole, an inhibitor of facilitated transport systems for purines and pyrimidines, was shown to enhance the toxicity of methotrexate (MTX) against cells in culture and in mice. Under certain incubation conditions, the availability of performed purines and pyrimidines in undialyzed serum appeared to render Chinese hamster ovary cells insensitive to MTX. Addition to the culture of nontoxic levels of dipyridamole conferred sensitivity to MTX. Inhibition of [3H]thymidine uptake by dipyridamole paralleled the enhanced MTX toxicity in a comparison of the dose-effect relationships. Inhibition of [3H]hypoxanthine uptake also occurred, although approximately 10-fold higher levels of dipyridamole were required. In vivo dipyridamole enhanced MTX toxicity in mice; however, the antitumor activity of MTX toward Ridgway osteogenic sarcoma and L1210 leukemia was not dramatically improved.
双嘧达莫是嘌呤和嘧啶易化转运系统的抑制剂，已证明它能增强甲氨蝶呤（MTX）对培养细胞和小鼠的毒性。在某些培养条件下，未透析血清中现成的嘌呤和嘧啶似乎使中国仓鼠卵巢细胞对MTX不敏感。向培养物中添加无毒水平的双嘧达莫可使细胞对MTX敏感。在剂量效应关系的比较中，双嘧达莫对[3H]胸腺嘧啶摄取的抑制与MTX毒性增强平行。对[3H]次黄嘌呤摄取的抑制也会发生，尽管所需双嘧达莫的水平约高10倍。在体内，双嘧达莫增强了MTX对小鼠的毒性；然而，MTX对里奇韦骨肉瘤和L1210白血病的抗肿瘤活性并未得到显著改善。
