Iodoacetic acid and related sulfhydryl reagents fail to inhibit cell-cell communication: mechanisms of immunotoxicity in vitro.
The present study was undertaken to examine the effects of iodoacetic acid, a non-phorbol tumor promoter, on metabolic cooperation between mutant human fibroblasts as measured by [14C]citrulline incorporation. Other thiol-reactive polyphenolic compounds such as hydroquinone and 2-hydroxyestrone were also examined. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumor promoter, inhibited the cell-cell communication by more than 60% at 20 ng/ml. However, iodoacetic acid, hydroquinone, and 2-hydroxyestrone, had no effect on the process even at cytotoxic concentrations. Induction of intercellular contact (agglutination) among lymphocytes during the course of phytohemagglutinin (PHA)-induced blastogenesis was monitored turbidometrically at 620 nm. Hydroquinone and 2-hydroxyestrone suppressed the PHA-induced lymphocyte agglutination at 1-2 microM in vitro concentrations while iodoacetic acid was devoid of any effects at concentrations up to 100 microM. Hydroquinone and 2-hydroxyestrone concomitantly suppressed PHA-induced lymphocyte blastogenesis at 1-2 microM in vitro concentrations while the suppression by iodoacetic acid was significant at 10 microM. All 3 compounds failed to disrupt microtubule assembly, a sulfhydryl-dependent process, in a rat brain crude extract. However, p-benzoquinone, an oxidation product of hydroquinone, did inhibit the process at 1 mM. In summary, these studies suggest that, unlike TPA, thiol-reactive non-phorbol tumor promoters and polyphenolic compounds do not inhibit cell-cell communication between mutant human fibroblasts. Although the compounds demonstrate diverse molecular mechanisms of action, they all inhibit in vitro immune functions suggesting that immunosuppression may play a role in tumor promotion.
D000371:Agglutination / Q000187:drug effects; D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000031:analogs & derivatives*; D005260:Female; D006873:Hydroquinones / Q000633:toxicity*; D006894:Hydroxyestrones / Q000633:toxicity*; D007210:Indoleacetic Acids / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008870:Microtubules / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology
D006873:Hydroquinones; D006894:Hydroxyestrones; D007210:Indoleacetic Acids; D010835:Phytohemagglutinins; D004970:Estrone; C030737:indoleacetic acid; D014442:Monophenol Monooxygenase; C024980:2-hydroxyestrone; C031927:hydroquinone