Selective increase of c‐myc mRNA levels by methylglyoxal‐bis (guanylhydrazone) and novobiocin in serum‐stimulated fibroblasts

We have studied the effect of methylglyoxal-bis (guanylhydrazone) (MGBG) and novobiocin on the accumulation of specific mRNAs in serum-stimulated ts13 cells (a temperature-sensitive mutant of the BHK cell line). The RNAs studied included: c-myc, v-ras, ornithine decarboxylase, beta-actin, histone H3, and those represented by clones p2F1 and p1B6 (Hirschhorn et al., Proc. Natl, Acad. Sci. USA, 81:6004, 1984) All these RNAs accumulated at higher levels when quiescent cells were serum stimulated for 16 h. Both MGBG (25 micronM and 100 micronM) and novobiocin (200 micrograms/ml) effectively prevented the transition from G0 to S phase. We found that 100 microM MGBG induced an overaccumulation of c-myc RNA while H3 RNA was decreased, and the steady-state levels of all other RNAs were the same as in cells stimulated without the drug. Novobiocin prevented the serum-induced increase in the amount of all RNAs, which remained at the same levels as in quiescent cells, with the exception of c-myc, which again accumulated at a higher level in drug-treated cells than in serum-stimulated untreated cells. The possible significance of these results is discussed.