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 /xg/ml) induces prolactin synthesis in these cells. BrdUrd also induces prolactin synthesis in F1BGH12C1 cells, a BrdUrd resistant (BrdUrd r) substrain isolated from GH12C1 cells. The F1BGH~2C1 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 BrdUrd r 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.KEY WORDS 5-bromodeoxyuridine prolactin gene expression 9 rat pituitary tumor ceilsThe drug 5-bromodeoxyuridine (BrdUrd), a thymidine analogue, seems to have diverse effects on the various processes of differentiation in eukaryotic cells. These may be classified into two distinct types. BrdUrd suppresses the synthesis of specific proteins in certain cells, and in other cell types the drug induces the production of certain cell-specific proteins. Rutter et al. (12) described in detail the role of BrdUrd on different eukaryotic cell systems. On the basis of the different effects of this drug, these authors discussed the possible DNA-linked and non-DNA-linked mechanisms of action of BrdUrd.Holtzer and Abbott (7) postulated that BrdUrd selectively inhibits the synthesis of luxury molecules without grossly depressing the synthesis of essential molecules of the cells. Priesler et al. (11) claimed that inhibition of differentiated function J. CELL BIOLOGY 9 The Rockefeller University Press 9
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