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