Effects of tumor promoters on the frequency of metallothionein I gene amplification in cells exposed to cadmium.
Three potent tumor promoters of different classes, 12-O-tetradecanoylphorbol-13-acetate, dihydroteleocidin B, and aplysiatoxin, and two moderate tumor promoters, mezerein and debromoaplysiatoxin, enhanced the frequency of appearance of cadmium-resistant Chinese hamster lung cells when the cells were exposed to cytotoxic levels of CdCl2. With these compounds, the activity to induce cadmium-resistant cells correlated well with the potency of tumor-promoting activity. Cadmium resistance, which persisted after removal of the tumor promoters, was associated with the overproduction of metallothionein I messenger RNA. The amplified metallothionein I genes were shown by Southern blotting experiments. The relevance of the gene amplification caused by tumor promoters is discussed in relation to cancer development and progression.
D000470:Alkaloids / Q000633:toxicity; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes; D005784:Gene Amplification / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D007783:Lactones / Q000633:toxicity; D008168:Lung; D008235:Lyngbya Toxins; D008668:Metallothionein / Q000235:genetics*; D008978:Mollusk Venoms / Q000633:toxicity; D010703:Phorbol Esters / Q000633:toxicity; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000470:Alkaloids; D002273:Carcinogens; D004224:Diterpenes; D007783:Lactones; D008235:Lyngbya Toxins; D008978:Mollusk Venoms; D010703:Phorbol Esters; D013729:Terpenes; D002104:Cadmium; C011309:mezerein; C017179:debromoaplysiatoxin; C006610:aplysiatoxin; D008668:Metallothionein; C022229:dihydroteleocidin B; D013755:Tetradecanoylphorbol Acetate