CHARACTERIZATION OF THE SUPERINDUCTION OF THE C-MYC PROTOONCOGENE IN FIBROBLASTS BY BENZAMIDE DERIVATIVES

In mouse fibroblasts stimulated from quiescence into proliferation by serum the induction of expression of the c-myc proto-oncogene is stron gly stimulated by 3-methoxybenzamide. Similar superinduction effects a re seen with related compounds such as 3-aminobenzamide and the acid a nalogues, 3-anisic acid and 3-aminobenzoic acid. Whereas the benzamide derivatives are inhibitors of poly(ADP-ribose) polymerase the acid an alogues are not, suggesting that inhibition of this enzyme is not the basis for superinduction of the c-myc gene. Analysis of the kinetics o f induction of c-myc mRNA indicates that the RNA accumulates more rapi dly as well as to a higher level in the presence of serum plus 3-metho xybenzamide than with serum alone. However the stimulation is transien t in both cases. Addition of actinomycin D at 30 min or 1 h after seru m stimulation shows the c-myc mRNA to be stable at these times, in the presence or absence of 3-methoxybenzamide. Thus the effect of the lat ter on c-myc mRNA accumulation is likely to be exerted at the level of transcription or RNA processing rather than turnover of the mRNA.