Changes in thymidine incorporation into tumor cells induced by supernatants of calcium-ionophore-treated macrophages incubated with tumor cells.
Thioglycollate-elicited peritoneal M phi of mice were treated with calcium ionophore A23187 prior to incubation with tumor cells. Supernatants prepared from the incubation mixtures were assayed for their effects on incorporation of 3H-thymidine into tumor cells. Significant inhibition of incorporation was observed in most instances. Ingestion of indomethacin in the drinking water for 7 days by prospective M phi donors increased the inhibition by supernatants. The activity of the supernatants was neither specific for the strain and sex of M phi donors nor correlated with the genotype of the tumors. The activity even crossed the species barrier inasmuch as inhibitory supernatants were produced by murine M phi incubated with either murine or human tumor cells. Supernatants derived from murine as well as human tumor cells significantly depressed thymidine incorporation into murine and human tumor cells, although there were some differences in the response of the two kinds of tumor cells. In rare instances, supernatants enhanced, rather than inhibited, thymidine incorporation. Moreover, when supernatants, added to tumor cells, were removed and replaced by fresh medium, in most instances, significant enhancement of thymidine incorporated occurred. The formation of both growth-inhibiting and growth-promoting factors by M phi in the in vitro model used in this study, may explain the dual role of M phi in neoplasia in vivo.
Stern
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Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical Center, P.O.B. 12272, Jerusalem 91 120, Israel.
Lein
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms; D013936:Thymidine / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D017077:Culture Media, Conditioned; D007476:Ionophores; D000001:Calcimycin; D013936:Thymidine