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单一烷化剂对正常外周血淋巴细胞的体外作用。

In vitro effects of single alkylating agents on normal peripheral blood lymphocytes.

作者信息

Brody J I

出版信息

J Lab Clin Med. 1979 Jul;94(1):114-122.

PMID:469367
Abstract

The separate in vitro effects of HN2 and L-PAM on resting and stimulated peripheral blood lymphocytes were evaluated with biochemical and morphologic experimental endpoints. Both alkylating agents caused dose-dependent reduction of protein, RNA, and DNA synthesis, but the patterns of diminution differed. The number of cells staining with Erythrosin B, as a toxicity indicator, also rose with higher drug concentrations, but a large proportion of lymphocytes remained unstained even at the maximum drug dose. Stimulation with PHA partially nullified the suppression caused by HN2 but did not influence the effects of L-PAM. Exposure to PWM rendered the in vitro HN2 innocuous but L-PAM remained cytotoxic. Simultaneous lectin-induced blastogenesis proceeded unaltered. Finally, comparisons between 72 and 4 hr drug exposures imply that interference with intracellular synthesis occurs promptly, continues after drug removal, and is related quantitatively to drug concentration rather than to duration of contact.

摘要

通过生化和形态学实验终点评估了 HN2 和左旋苯丙氨酸氮芥(L-PAM)对静息和刺激外周血淋巴细胞的体外单独作用。两种烷化剂均导致蛋白质、RNA 和 DNA 合成呈剂量依赖性减少,但减少模式不同。作为毒性指标,用赤藓红 B 染色的细胞数量也随药物浓度升高而增加,但即使在最大药物剂量下,仍有很大比例的淋巴细胞未被染色。用植物血凝素(PHA)刺激部分抵消了 HN2 引起的抑制作用,但不影响 L-PAM 的作用。暴露于美洲商陆有丝分裂原(PWM)使体外的 HN2 无害,但 L-PAM 仍具有细胞毒性。同时,凝集素诱导的细胞增殖未受影响。最后,72 小时和 4 小时药物暴露的比较表明,对细胞内合成的干扰迅速发生,在药物去除后仍持续存在,并且在数量上与药物浓度而非接触持续时间有关。

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