/V,/V-Dimethylformamide and Sodium Butyrate Modulation of the Activities of Purine-metabolizing Enzymes in Cultured Human Colon Carcinoma Cells1

The specific activities of 11 purine-metabolizing enzymes were assayed in three cultured human colon carcinoma cell lines, HCT-15 and the A and D clones of the heterogeneous DLD-1 line. Enzyme activities were also determined for each of the cell lines cultivated in the presence of either of two com pounds known to induce differentiation in tumor cells: the polar solvent A/,A/-dimethylformamide and sodium butyrate. The ac tivities of three enzymes, purine nucleoside phosphorylase, 5'- deoxy-5'-methylthioadenosine phosphorylase, and nucleoside diphosphokinase were not changed by exposure to dimethyl- formamide or butyrate. Xanthine oxidase activity was not de tectable in any of the lines and was not inducible by either compound. Expression of seven other enzymes was modulated more than three-fold in at least one line by one or both agents. These enzymes include adenine and hypoxanthine-guanine phosphoribosyltransferases, adenosine kinase, adenosine de- aminase, guanine deaminase, and guanosine and adenosine monophosphate kinases. Although both agents induce differ entiation, striking differences in the patterns of enzyme modu lations were observed. The effects were cell line dependent as well as agent dependent. Guanine deaminase activity in HCT- 15 cells increased six-fold upon exposure to butyrate, whereas it decreased three-fold in clone D cells in response to dimethyl- formamide. Adenosine deaminase activity in dimethylformam- ide-treated clone A cells was decreased 11-fold compared to that determined for untreated cells. Therefore, some human colon tumor cells treated with dimethylformamide could be more sensitive to adenosine analogs such as formycin and 8- azaadenosine, which are good substrates for adenosine de aminase. These results support the concept that relatively nontoxic differentiation-inducing compounds might potentiate the effects of antineoplastic drugs.