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.
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Authors | E C Si, R W Pfeifer, G K Yim |
Journal | Toxicology
(Toxicology)
Vol. 44
Issue 1
Pg. 73-89
(Apr 1987)
ISSN: 0300-483X [Print] Ireland |
PMID | 3105120
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Hydroquinones
- Hydroxyestrones
- Indoleacetic Acids
- Phytohemagglutinins
- Estrone
- indoleacetic acid
- Monophenol Monooxygenase
- 2-hydroxyestrone
- hydroquinone
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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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