Biswas D K, Abdullah K T, Brennessel B A
J Cell Biol. 1979 Apr;81(1):1-9. doi: 10.1083/jcb.81.1.1.
GH12C1, a clonal strain of rat pituitary tumor cells in culture (GH cells), does not produce detectable amounts of prolactin. 5-Bromodeoxyuridine (BrdUrd), the thymidine analogue, at sublethal concentrations (3-5 microgram/ml) induces prolactin synthesis in these cells. BrdUrd also induces prolactin synthesis in F1BGH12C1 cells, a BrdUrd resistant (BrdUrdr) substrain isolated from GH12C1 cells. The F1BGH12C1 strain is not drug dependent, but its resistance to BrdUrd is a stable phenotype. The significant features of the induction of prolactin synthesis in the BrdUrdr strain are the increased net synthesis of prolactin and the shortening of the lag period of prolactin induction. As BrdUrd concentration in the growth medium is increased, the rise in prolactin synthesis parallels the increased incorporation of BrdUrd into DNA. Prolactin synthesis is first detected when BrdUrd replaces 20-25% of the thymidine in DNA. BrdUrd can replace up to 75-80% of the thymidine within 2 d of treatment. Partial starvation of these cells under specified growth conditions does not affect the general growth pattern of the cells, general protein synthesis, and thymidine uptake, but does affect DNA synthesis. When cells are cultured under conditions in which DNA synthesis is preferentially inhibited, BrdUrd does not induce prolactin synthesis, suggestive of a DNA-mediated mechanism of action for the drug.
GH12C1是培养的大鼠垂体肿瘤细胞的克隆株（GH细胞），不产生可检测量的催乳素。胸腺嘧啶类似物5-溴脱氧尿苷（BrdUrd）在亚致死浓度（3-5微克/毫升）时可诱导这些细胞合成催乳素。BrdUrd还可诱导从GH12C1细胞分离出的BrdUrd抗性（BrdUrdr）亚株F1BGH12C1细胞合成催乳素。F1BGH12C1株不依赖药物，但其对BrdUrd的抗性是一种稳定的表型。BrdUrdr株中催乳素合成诱导的显著特征是催乳素净合成增加以及催乳素诱导的延迟期缩短。随着生长培养基中BrdUrd浓度的增加，催乳素合成的增加与BrdUrd掺入DNA的增加平行。当BrdUrd取代DNA中20-25%的胸腺嘧啶时，首次检测到催乳素合成。在处理2天内，BrdUrd可取代高达75-80%的胸腺嘧啶。在特定生长条件下对这些细胞进行部分饥饿处理不会影响细胞的总体生长模式、总体蛋白质合成和胸腺嘧啶摄取，但会影响DNA合成。当细胞在优先抑制DNA合成的条件下培养时，BrdUrd不会诱导催乳素合成，提示该药物的作用机制是由DNA介导的。
