Marz R, Wohlhueter R M, Plagemann P G
J Membr Biol. 1977 Jun 6;34(2-3):277-88. doi: 10.1007/BF01870304.
Novikoff rat hepatoma cells were propagated in suspension culture in the presence of 1 micron methotrexate and various concentrations of hypoxanthine (or adenosine plus guanosine) and thymidine and with or without the inhibitor of nucleoside and purine transport, Persantin (dipyridamole). Methotrexate-treated cells failed to replicate and died even if the medium was supplemented with either thymidine or a purine source, but normal replication occurred when both were present. The additional presence of Persantin reduced the rate of transport of thymidine or hypoxanthine and thus their incorporation into the nucleotide pool and decreased the rate of cell replication. The growth rate of the cells was directly proportional to the rate of incorporation of thymidine (in the presence of excess hypoxanthine) or of hypoxanthine (in the presence of excess thymidine) until the normal maximum growth rate was obtained. Normal cell replication in the presence of methotrexate and Persantin occurred only when the medium was supplemented with 500 micron hypoxanthine and 30 micron thymidine. The results illustrate a dependence of the growth rate of mammalian cells on the rate of transport of essential nutrients into the cell.
将诺维科夫大鼠肝癌细胞在含有1微摩尔甲氨蝶呤以及不同浓度次黄嘌呤（或腺苷加鸟苷）和胸腺嘧啶核苷的悬浮培养液中进行培养，并添加或不添加核苷和嘌呤转运抑制剂潘生丁（双嘧达莫）。即使在培养液中添加胸腺嘧啶核苷或嘌呤来源，经甲氨蝶呤处理的细胞也无法复制并死亡，但当两者都存在时则会发生正常复制。额外添加潘生丁会降低胸腺嘧啶核苷或次黄嘌呤的转运速率，从而减少它们掺入核苷酸池的量，并降低细胞复制速率。在获得正常最大生长速率之前，细胞的生长速率与胸腺嘧啶核苷（在次黄嘌呤过量的情况下）或次黄嘌呤（在胸腺嘧啶核苷过量的情况下）的掺入速率成正比。只有当培养液中添加500微摩尔次黄嘌呤和30微摩尔胸腺嘧啶核苷时，在甲氨蝶呤和潘生丁存在的情况下细胞才会正常复制。这些结果表明哺乳动物细胞的生长速率依赖于必需营养物质进入细胞的转运速率。
