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By Fazal Ahmad (Eds.)

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47 2 3 . H o w a r d , Β . V. , H o w a r d , W. J . , D e l à L i e r a , M. a n d K e f a l i d e s , N . A . , A t h e r o s c l e r o s i s , 23 (1976) 5 2 1 . 2 4 . J u n g a s , R. L. and B a l l , E . G . , 1696. 25. K o r n , E. D. , J. Biol. , 2 6 . K u r i - H a r c u c h , W. a n d G r e e n , (1977) 2158. Biochemistry, 2 1 5 ( 1 9 5 5 ) 1. Η. , J . Biol. Mackall, J. C , Student, A . K . , Polakis, S . E . , M . D . , J. Biol. C h e m . , 251 (1976) 6462. 28. Mackall, Res. 3 (1964) J .

However, an increase in the concentration of the inducer of the lac Operon is sufficient to reverse the BrdUrd effect on repressor binding. Thus, BrdUrd-DNA and inducer can be thought of as competitors for repressor. BrdUrd leads to higher affinity of the repressor for DNA but the inducer at higher concentrations than required in unsubstituted DNA can compete with and remove the repressor from the DNA. It is apparent that the replacement of the methyl group in the 5 42 THOMAS R. RUSSELL position of thymidine with bromine leads to higher affinity of a regulatory protein to DNA.

MeiBuXan, nevertheless, is a very potent stimulator of the process. MeiBu-Xan may function as an inducer of differentiation independent of the cyclic nucleotides. It is of interest that numerous purine derivatives structurally similar to MeiBu-Xan have been shown to induce the differentiation of erythroleukemia cells into hemoglobin producing cells ( 1 5 ) . 0 in control cultures to 4 in MeiBu-Xan treated cultures. Thus, in three experimental systems, the conversion of 3T3-L fibroblasts into adipose cells, of erythroleukemia cells into hemoglobin producing cells and of precursor stem cells into granulocytes structurally similar purine derivatives (all closely related to hypoxanthine) are able to accelerate a differentiation process.

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