Chemical carcinogens induce cadmium resistance and activate metallothionein genes in cadmium sensitive S49 mouse cells.
Treatment of cadmium-sensitive (Cds) metallothionein-negative S49 mouse cells with two direct-acting chemical carcinogens (N-ethylnitrosourea or N-acetoxy-2-acetylamino-fluorene) or with u.v. radiation induced a large increase in phenotypically stable cadmium-resistant (Cdr) variants. In contrast, treatment with any of three agents which alkylate proteins (N-ethylmaleimide, iodoacetate, or phenylmethyl-sulfonyl fluoride) was without effect. Similarly, treatment with 2-acetylaminofluorene (a pre-carcinogen) or with 12-O-tetradecanoylphorbol-13-acetate (a tumor promoter) did not result in an increase in Cdr variants. Initial studies indicate that in many variants the metallothionein-I gene, the metallothionein-II gene, or both have been activated. Thus the induction of cadmium resistance in Cds cells is a potentially useful system to explore the activation of quiescent genes by carcinogens.
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D004351:Drug Resistance; D004794:Enzyme Repression; D005038:Ethylnitrosourea / Q000494:pharmacology; D005796:Genes; D066298:In Vitro Techniques; D008223:Lymphoma / Q000235:genetics*; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D011831:Radiation Genetics; D013601:T-Lymphocytes; D014466:Ultraviolet Rays
D002273:Carcinogens; D002104:Cadmium; D000099:Acetoxyacetylaminofluorene; D008668:Metallothionein; D005038:Ethylnitrosourea