Kleinerman E S, Zwelling L A, Schwartz R, Muchmore A V
Cancer Res. 1982 May;42(5):1692-5.
We have shown previously that cis-diamminedichloroplatinum(II) (cis-DDP), an active antineoplastic agent, and X-irradiation enhanced human spontaneous monocyte-mediated cytotoxicity in vitro. To ascertain whether this is a unique property of cis-DDP or common to other effective antineoplastic agents, we studied the effect of L-phenylalanine mustard (L-PAM), Adriamycin (ADR), actinomycin D, and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) on spontaneous monocyte-mediated cytotoxicity, cis-DDP, ADR, L-PAM, and m-AMSA under appropriate in vitro conditions all increased spontaneous monocyte-mediated cytotoxicity. Activation involved (a) direct monocyte activation (cis-DDP and ADR); (b) inactivation of suppressor lymphocytes (X-irradiation); (c) a combination of the two (L-PAM); or (d) mechanisms not yet elucidated (m-AMSA). In contrast, incubating mononuclear leukocytes with 0.4 microgram actinomycin D per ml depressed monocyte-mediated killing. Thus, while stimulation of "nonspecific" killing is not a unique property of cis-DDP, it is not a universal effect of all chemotherapy agents. The stimulation and enhancement of already existing host defense mechanisms may be an important additional way in which many chemotherapeutic agents exert their antitumor effect.
我们之前已经表明，顺二氯二氨铂（II）（顺铂），一种活性抗肿瘤药物，与X射线照射在体外可增强人类自发单核细胞介导的细胞毒性。为了确定这是顺铂的独特性质还是其他有效抗肿瘤药物共有的性质，我们研究了L-苯丙氨酸氮芥（L-PAM）、阿霉素（ADR）、放线菌素D和4'-（9-吖啶基氨基）甲磺酰间氨基苯甲醚（m-AMSA）对自发单核细胞介导的细胞毒性的影响。在适当的体外条件下，顺铂、阿霉素、L-PAM和m-AMSA均增加了自发单核细胞介导的细胞毒性。激活涉及（a）直接单核细胞激活（顺铂和阿霉素）；（b）抑制性淋巴细胞失活（X射线照射）；（c）两者结合（L-PAM）；或（d）尚未阐明的机制（m-AMSA）。相反，将单核白细胞与每毫升0.4微克放线菌素D一起孵育会抑制单核细胞介导的杀伤作用。因此，虽然刺激“非特异性”杀伤不是顺铂的独特性质，但也不是所有化疗药物的普遍作用。刺激和增强已有的宿主防御机制可能是许多化疗药物发挥抗肿瘤作用的重要额外方式。
