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As measured by a decreased rate of dissociation, lac repressor binds 10-times tighter to 5-bromodeoxyuridine-substituted lac operator than it does to normal lac operator. This result is obtained both in the absence and in the presence of isopropylthiogalactoside, an inducing ligand. These data are significant with regard to the mechanism of sequence-specific protein-DNA interaction, and also suggest a possible explanation for the effects of bromodeoxyuridine on the expression of differentiated functions in eukaryotic cells. Recently, the effect of BrdU on eukaryotic cells has received a great deal of attention, and. our results may be relevant to this work. BrdU selectively blocks the expression of differentiated functions. In the presence of BrdU, presumptive myoblasts do not form myotubes or striated myofibrils (3, 4). Chondrocytes cease production of cartilage enzymes (5, 6), melanoma cells cease pigment production (7), and amnion cells cease mucopolysaccharide synthesis (8). This analogue also blocks the expression of the differentiated phenotype in cultures of pancreatic tissue (9, 10), and prevents the induction of tyrosine aminotransferase in hepatoma cells (11). As pointed out by Holtzer and Abbott (12), BrdU appears to suppress selectively the synthesis of "luxury" molecules without grossly depressing the synthesis of "essential" molecules. Within the last year, several groups have also reported (13)(14)(15)(16)(17)(18)

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