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

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Abstract
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, β‐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 μM and 100 μM) and novobiocin (200 μg/ml) effectively prevented the transition from G0 to S phase. We found that 100 μM 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.