Straw J A, Talbot D C, Taylor G A, Harrap K R
J Natl Cancer Inst. 1977 Jan;58(1):91-7. doi: 10.1093/jnci/58.1.91.
Thymidine, in the absence of hypoxanthine, failed to protect normal mice from the acute toxicity of methotrexate, though tumor-bearing animals could be protected with thymidine alone, probably as a result of the availability of DNA degradation products released from drug-sensitive tumor cells. Although metrotrexate induced an early purine deficiency in gut cells, this effect was not detected in bone marrow. Later, purine deficiency became apparent in the gut and bone marrow of methotrexate-treated animals.
在缺乏次黄嘌呤的情况下，胸苷无法保护正常小鼠免受甲氨蝶呤的急性毒性影响，尽管荷瘤动物仅用胸苷就能得到保护，这可能是由于对药物敏感的肿瘤细胞释放出DNA降解产物所致。虽然甲氨蝶呤在肠道细胞中诱导了早期嘌呤缺乏，但在骨髓中未检测到这种效应。后来，嘌呤缺乏在接受甲氨蝶呤治疗的动物的肠道和骨髓中变得明显。
