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Effect of L-Phenylalanine Mustard, Adriamycin, Actinomycin D, and 4'-(9-Acridinylamino)methanesulfon-m-anisidide on Naturally Occurring Human Spontaneous Monocyte-mediated Cytotoxicity

Mononuclear Phagocyte Section, Biological Response Modifiers Program, Biological Research and Therapy Branch, Division of Cancer Treatment, Frederick, Maryland 21701 [E. S. K.]; the Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, Bethesda, Maryland 20205 [L. A. Z.]; and the Metabolism Branch, Division of Cancer Biologics and Diagnosis [R. S., A. V. M.], National Cancer Institute, NIH, Bethesda, Maryland 20205

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 µg actinomycin D per ml depressed monocytemediated killing.

Thus, while stimulation of "nonspecific" killing is not a unique property of cis-DDP, it is not a universal effect of all chemotherapeutic 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.

¹ To whom requests for reprints should be addressed, at the Basic Mechanism Section, Biological Response Modifiers Program, Building 426, National Cancer Institute-Frederick Cancer Research Facility, Frederick, Md. 21701.

Received 11/ 4/81. Accepted 2/ 8/82.

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