Metallothioneins (MTs) are induced in cultured cells and experimental animal tissues by a variety of chemical agents. We report that whole-body X irradiation (1 to 80 Gy) induces MT-1 mRNA transcription and protein expression and accumulation in liver but not in kidney or spleen. The degree of induction was comparable to maximum levels achieved after treatment with metal salts, but the peak of MT-1 mRNA and protein accumulation was approximately 10 h later than with treatment with metal salts and remained high for an extended period. Because of the lack of induction of MT-1 by X rays in cultured cells, and the similarity of the tissue pattern of MT induction between X rays and other agents that also do not induce MT expression in cultured cells, it appears that these agents may act through the mediation of tissue-specific factors. The implications of radiation-induced metallothionein synthesis and organ-specific resistance to cellular damage are discussed.

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