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Iodoacetic acid and related sulfhydryl reagents fail to inhibit cell-cell communication: mechanisms of immunotoxicity in vitro.

Abstract
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.
AuthorsE C Si, R W Pfeifer, G K Yim
JournalToxicology (Toxicology) Vol. 44 Issue 1 Pg. 73-89 (Apr 1987) ISSN: 0300-483X [Print] Ireland
PMID3105120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Hydroquinones
  • Hydroxyestrones
  • Indoleacetic Acids
  • Phytohemagglutinins
  • Estrone
  • indoleacetic acid
  • Monophenol Monooxygenase
  • 2-hydroxyestrone
  • hydroquinone
Topics
  • Agglutination (drug effects)
  • Animals
  • Cell Communication (drug effects)
  • Dose-Response Relationship, Drug
  • Estrone (analogs & derivatives)
  • Female
  • Hydroquinones (toxicity)
  • Hydroxyestrones (toxicity)
  • Indoleacetic Acids (toxicity)
  • Lymphocyte Activation (drug effects)
  • Mice
  • Mice, Inbred Strains
  • Microtubules (drug effects)
  • Monophenol Monooxygenase (pharmacology)
  • Phytohemagglutinins (pharmacology)

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