Increase in frequency of appearance of cadmium-resistant cells induced by various tumor promoters; evidence for the induction of gene amplification.
When Chinese hamster lung (CHL) cells were cultured in medium containing 25 microM cadmium chloride, resistant cells appeared at a frequency of 0.04%. When one of three tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA), aplysiatoxin and dihydroteleocidin B, was added during selection with cadmium chloride, the frequency of appearance of resistant cells increased more than 50-fold. Two of the resistant clones obtained were characterized. Both clones produced much higher levels of metallothionein I mRNA than the parental CHL cells. Southern blot analysis showed that in these resistant cells, metallothionein I genes were amplified approximately 5-fold. Therefore, it seems that tumor promoters can enhance the frequency of gene amplification. One possible mechanism of the action of tumor promoters in oncogenesis is amplification of activated c-onc genes. Consistent with this idea, it has been reported that c-onc genes are amplified in various cancer cells. We also found that the c-Ha-ras and c-myc genes were amplified in a bladder cancer removed surgically and in a transplanted rat hepatocellular carcinoma, Morris hepatoma 7794A, respectively.
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D005784:Gene Amplification / Q000187:drug effects*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D009857:Oncogenes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D002273:Carcinogens; D002104:Cadmium; D008668:Metallothionein; D013755:Tetradecanoylphorbol Acetate