Reversible suppression of c-myc expression in a human colon carcinoma line by the anticancer agent N-methylformamide.

The anticancer agent N-methylformamide (NMF), which at high concentrations (170 mM) induces cultured DLD-1 Clone A human colon carcinoma cells to increase their doubling times and lose their tumorigenicity in nude mice (Cordeiro, R.F., and Savarese, T.M. Cancer Res., 46: 1297-1305, 1986), suppresses the expression of the c-myc protooncogene in these cells in a dose- and time-dependent manner. This suppression involves an inhibition of c-myc transcription rather than an increased degradation of c-myc mRNA, and is reversed if NMF is removed from the culture medium. Expression of the glyceraldehyde 3-phosphate dehydrogenase gene, which is thought to be constitutive, is phosphate dehydrogenase gene, which is thought to be constitutive, is relatively unaffected by NMF treatment. The NMF-mediated decrease in c-myc expression may be associated with the ability of this agent to increase the doubling time of these cells, but there is no direct temporal link between the loss of c-myc expression and the NMF-induced loss of tumorigenicity.