Kajander E O, Harvima R J, Kauppinen L, Akerman K K, Martikainen H, Pajula R L, Kärenlampi S O
Department of Biochemistry, University of Kuopio, Finland.
Biochem J. 1990 May 1;267(3):767-74. doi: 10.1042/bj2670767.
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.
研究了硒代蛋氨酸（SeMet）对17种培养细胞系生长的影响。三种肝癌细胞系培养基中的SeMet在亚细胞毒性水平（1 - 20 microM）促进细胞生长，但未刺激恶性淋巴细胞和髓细胞的生长。培养3 - 10天后检测发现，L - SeMet对所有17种细胞系均具有细胞毒性。在含有100 microM - 蛋氨酸的培养基中，30 - 160 microM - SeMet可导致50%的生长抑制。SeMet对正常细胞（成纤维细胞）和恶性细胞的细胞毒性相当相似，不具有特异性抗肿瘤细胞毒性。降低蛋氨酸浓度会增加细胞毒性。SeMet的DL形式比L形式的细胞毒性小。在恶性R1.1淋巴母细胞中，L - SeMet代谢为S - 腺苷甲硫氨酸的硒类似物的效率与天然硫类似物蛋氨酸大致相同。同时，S - 腺苷甲硫氨酸池减少。这一现象在早期且在细胞毒性SeMet水平时就会发生。SeMet处理未改变蛋氨酸腺苷转移酶活性。ATP池早期未受影响，DNA和蛋白质合成的减少发生较晚，且显然与细胞死亡有关。在低细胞毒性SeMet水平下，24小时可轻微刺激RNA合成，但48小时后则受到明显抑制。S - 腺苷甲硫氨酸的SeMet类似物可有效地用于特定的酶促转甲基作用。在处理过的细胞中未积累S - 腺苷高半胱氨酸及其硒类似物。这些发现共同表明S - 腺苷甲硫氨酸代谢直接或间接参与了SeMet的细胞毒性作用，但排除了转甲基作用的严重受阻。
