Modulation of proto-oncogene expression by polychlorinated biphenyls in 3T3-L1 cell line.
The effects of two substituted polychlorinated biphenyls, the 3,4,5,3',4,5' (PCB-169) and the 2,3,4,2',4',5' (PCB-138) forms, were examined on the expression of c-myc, c-jun, c-ras, and jun-b in 3T3-L1 cells. Northern blot analysis demonstrated that the two PCBs, which exhibit a coplanar and di-ortho-substituted configuration, activated these oncogenes differently. PCB-138 markedly induced overexpression of ras, jun, and myc, whereas PCB-169 led to the overexpression of jun-b. High-performance liquid chromatography analysis of the cell samples treated in medium without serum revealed a higher intracellular concentration of the 2,3,4,2',4',5'-hexachlorobiphenyl (hexaCB), whereas the 3,4,5,3',4'5'-hexaCB reached the same concentration in the sonicated samples of cells with or without serum. These results indicated that there was a relationship between PCB structure, bioavailability, and the capacity to stimulate oncogene expression.
European Centre for the Validation of Alternative Methods-J.R.C., Ispra, Italy.
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Gribaldo
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Sacco
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Casati
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Zucchi
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Dosanjh
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Catalani
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Marafante
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D015342:DNA Probes; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000633:toxicity*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D018631:ras Proteins / Q000096:biosynthesis*
D015342:DNA Probes; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; C029790:2,2',3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls; D018631:ras Proteins; C027309:3,4,5,3',4',5'-hexachlorobiphenyl