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Effects of selenomethionine on cell growth and on S-adenosylmethionine metabolism in cultured malignant cells.
Kajander, E O; Harvima, R J; Kauppinen, L; Akerman, K K; Martikainen, H; Pajula, R L; Kärenlampi, S O.
Afiliación
  • Kajander EO; Department of Biochemistry, University of Kuopio, Finland.
Biochem J ; 267(3): 767-74, 1990 May 01.
Article en En | MEDLINE | ID: mdl-2339986
The effects of selenomethionine (SeMet) on the growth of 17 cultured cell lines were studied. SeMet in the culture medium of three hepatoma cell lines promoted cell growth at subcytotoxic levels (1-20 microM), but the growth of malignant lymphoid and myeloid cells was not stimulated. L-SeMet was cytotoxic to all 17 cell lines when assayed after culture for 3-10 days. A 50% growth inhibition was observed by 30-160 microM-SeMet in a culture medium containing 100 microM-methionine. SeMet cytotoxicity to normal (fibroblasts) and malignant cells was rather similar, excluding specific antineoplastic cytotoxicity. Cytotoxicity was increased by decreasing concentrations of methionine. The DL form of SeMet was less cytotoxic than the L form. L-SeMet was metabolized to a selenium analogue of S-adenosylmethionine approximately as effectively as the natural sulphur analogue methionine in malignant R1.1 lymphoblasts. Concomitantly, S-adenosylmethionine pools were decreased. This occurred early and at cytotoxic SeMet levels. Methionine adenosyltransferase activity was not altered by SeMet treatment. ATP pools were not affected early, and decreases in the synthesis of DNA and protein took place late and were apparently related to cell death. RNA synthesis was slightly stimulated at low cytotoxic SeMet levels by 24 h, but was markedly inhibited after 48 h. The SeMet analogue of S-adenosylmethionine could be effectively utilized in a specific enzymic transmethylation. Neither S-adenosylhomocysteine nor its selenium analogue accumulated in the treated cells. These findings together suggest a direct or indirect involvement of S-adenosylmethionine metabolism in SeMet cytotoxicity, but exclude a gross blockage of transmethylations.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Selenio / Selenometionina Límite: Humans Idioma: En Revista: Biochem J Año: 1990 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Selenio / Selenometionina Límite: Humans Idioma: En Revista: Biochem J Año: 1990 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido