C-myc expression is maintained during the G1 phase cell cycle block produced by beryllium.
Salts of the toxic metal beryllium have been shown previously to prevent the synthesis of several enzymes essential for DNA replication in proliferating rat hepatic cells in vivo, and to inhibit the division of rat liver-derived BL9L epithelial cells in vitro, specifically during the G1 phase of the cell cycle. The present study shows, however, that exposure of serum-stimulated sub-confluent monolayer cultures of synchronized BL9L cells to inhibitory concentrations of the beryllium salt BeSO4 (50 microM) did not impair expression of the cell proliferation associated nuclear proto-oncogene c-myc. On the contrary, the increased c-myc mRNA levels normally observed during the G1 phase were maintained by continuous exposure of the cells to BeSO4. This response was specific in that other colloid forming metal salts (ZnSO4 and ZrSO4), which did not inhibit cell division, had no affect on c-myc expression, and mRNA levels for the constantly expressed H-2Kb major histocompatibility complex gene (3'Kb) were unaltered by BeSO4 treatment of the cells. The prevention by Be2+ of the down-regulation of c-myc expression in serum-stimulated BL9L cells appears to result from a modulation of the endogenous transcriptional control process for c-myc, which allows a maintained expression of the gene.
Skilleter
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MRC Toxicology Unit, BIBRA, Carshalton, Surrey, UK.
Barrass
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NC
Price
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RJ
D000818:Animals; D001608:Beryllium / Q000494:pharmacology*; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D051381:Rats; D015032:Zinc / Q000494:pharmacology; D015040:Zirconium / Q000494:pharmacology
D016271:Proto-Oncogene Proteins c-myc; D015040:Zirconium; D015032:Zinc; D001608:Beryllium