Zielke H R
Cancer Res. 1979 Sep;39(9):3373-6.
Malignant cells have enhanced sensitivity to inhibition of growth by thymidine. Cell growth of the permanent lymphoid cell line CCRF-CEM, originating from a patient with acute lymphoblastic leukemia, is inhibited by 3 x 10(-5) M thymidine, compared to 1 to 5 x 10(-3) M thymidine required to inhibit growth of normal lymphoid lines. Thymidine-resistant cells were isolated at a frequency of approximately 1/100,000 cells after cloning CCRF-CEM cells in medium containing 5 x 10(-4) M thymidine. The resistant cells lacked the enzyme thymidine kinase, had a 20-fold decrease of thymidine uptake, and were resistant to 1 x 10(-4) M 5-bromo-2-deoxyuridine. The cells were sensitive to 1 x 10(-5) M methotrexate, even in the presence of exogenously added thymidine and hypoxanthine. The data indicate that a small fraction of malignant cells may escape the toxic effect of high thymidine therapy and therefore, require additional chemotherapy for their control.
恶性细胞对胸腺嘧啶抑制生长的作用更为敏感。源自一名急性淋巴细胞白血病患者的永久性淋巴样细胞系CCRF - CEM的细胞生长，在3×10⁻⁵ M胸腺嘧啶作用下受到抑制，而正常淋巴样细胞系生长受抑制则需要1至5×10⁻³ M胸腺嘧啶。在含有5×10⁻⁴ M胸腺嘧啶的培养基中克隆CCRF - CEM细胞后，以约1/100,000细胞的频率分离出了胸腺嘧啶抗性细胞。抗性细胞缺乏胸腺嘧啶激酶，胸腺嘧啶摄取减少20倍，并且对1×10⁻⁴ M 5 - 溴 - 2 - 脱氧尿苷具有抗性。这些细胞对1×10⁻⁵ M甲氨蝶呤敏感，即使在外源添加胸腺嘧啶和次黄嘌呤的情况下也是如此。数据表明一小部分恶性细胞可能逃避高剂量胸腺嘧啶治疗的毒性作用，因此需要额外的化疗来控制它们。
