Effect of L-phenylalanine mustard, adriamycin, actinomycin D, and 4'-(9-acridinylamino)methanesulfon-m-anisidide on naturally occurring human spontaneous monocyte-mediated cytotoxicity.
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.
D000609:Aminoacridines / Q000494:pharmacology; D000677:Amsacrine; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008558:Melphalan / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine; D003609:Dactinomycin; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan