Inhibition of macrophage-induced tumor cell cytostasis and cytolysis by tumor-promoting phorbol diesters.
The effects of 3 tumor-promoting phorbol diesters and the corresponding inactive polyol phorbol on cytostatic and cytolytic activities of activated murine peritoneal macrophages toward target tumor cells derived from skin cells of the same species were examined. In both cases the diesters, without showing concurrent toxicity, considerably suppressed in dose-related fashion, the activity of the macrophages at concentrations active in promotion in vivo, being active even in nanogram quantities. The order of activity among different diesters for cytostasis or cytolysis was the same as that observed toward tumor promotion in mouse skin. The non-promoter phorbol was inactive in all instances. These findings concur with proposals for an important role for abrogation of normal antitumor defense mechanisms in promotion of mouse skin carcinogenesis by active phorbol diesters.
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced / Q000276:immunology*; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*
D010703:Phorbol Esters; D010704:Phorbols