Studies on the Modulating Effects of Retinoic Acid and Retinol Acetate Using Dye Transfer and Metabolic Cooperation Assays

MERCIER, T.; Honikman-Leban, E.; CHAUMONTET, C.; MARTEL, P.; Shahin, Majdi M.

doi:10.1093/toxsci/21.3.270

Cited by 5 publications

(8 citation statements)

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“…Some tumor promoters or their metabolites that act via the inhibition of cell-to-cell communication have been reported to enhance such activity at lower doses, showing the biphasic dose-response features of hormesis [122][123][124][125]. These data suggest that promoters may have the potential to reduce tumor promotion at lower doses while enhancing the process of carcinogenesis at higher doses.…”

Section: Do Tumor Promoters Act Hormetically?mentioning

confidence: 99%

Hormesis: Why it is Important to Toxicology and Toxicologists

Calabrese¹

2007

Environ Toxicol Chem

214

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This article provides a comprehensive review of hormesis, a dose-response concept that is characterized by a low-dose stimulation and a high-dose inhibition. The article traces the historical foundations of hormesis, its quantitative features and mechanistic foundations, and its risk assessment implications. The article indicates that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations. The hormetic dose response is highly generalizable, being independent of biological model, endpoint measured, chemical class, and interindividual variability. Hormesis also provides a framework for the study and assessment of chemical mixtures, incorporating the concept of additivity and synergism. Because the hormetic biphasic dose response represents a general pattern of biological responsiveness, it is expected that it will become progressively more significant within toxicological evaluation and risk assessment practices as well as have numerous biomedical applications.

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Section: Do Tumor Promoters Act Hormetically?mentioning

confidence: 99%

Hormesis: Why it is Important to Toxicology and Toxicologists

Calabrese¹

2007

Environ Toxicol Chem

214

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“…22 Numerous additional experiments were performed to estimate the mean stimulation factor and to analyse the distribution of the number of dye-coupled cells after microinjection.…”

Section: Junctional Transfermentioning

confidence: 99%

Retinoic acid enhances connexin43 expression at the post‐transcriptional level in rat liver epithelial cells

Bex¹,

Mercier²,

Chaumontet³

et al. 1995

Cell Biochemistry & Function

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The mechanism by which all-trans retinoic acid (RA) stimulates gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line. IAR203, was investigated. When RA, at 0.1 microM for 24-48 h, enhanced the dye transfer in IAR203 cells (x 1.4), it increased the amount of connexin43 (Cx43) in the cell-cell contact regions of the plasma membrane, as evidenced by analysis by Western blot and by immunofluorescence. It had no effect on the level of Cx43 mRNA. Freeze-fracture analysis of the size of gap junctions revealed an increase of the proportion of small gap junctions in RA-treated cells. We conclude that, in IAR203 cells, RA stimulates GJIC by acting at the post-transcriptional level of Cx43 regulation. The possibility that RA acts indirectly on the regulation of Cx43 expression, and increases the half-life of Cx43 by inducing adhesion molecules is discussed.

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“…To test the ability of flavonoids to modulate metabolic cooperation, alone or in combination with a tumor promoter (TPA), a modified procedure was used (34). Four hours after the cells were plated, flavonoids at 5,10, or 25 uM (dissolved in DMSO, 0.2% final concn) were added to the medium, with or without TPA (0.3 ng/ml) for 48 hours.…”

Section: Metabolic Cooperation Assaymentioning

confidence: 99%

“…The first, based on the measure of the dye transfer in an REL cell line, is sensitive to GJIC inhibitors and stimulators (34,38,42). The second, evaluating the metabolic cooperation of V79 hamster lung fibroblasts, permits the detection of inhibitory effects and modulating effects (synergy or antagonism) toward TPA-induced inhibition (34). The four flavonoids were studied with these two assays in the same range of concentrations.…”

Section: In Vitro Gijc Studiesmentioning

confidence: 99%

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Lack of tumor‐promoting effects of flavonoids: Studies on rat liver preneoplastic foci and onin vivoandin vitrogap junctional intercellular communication

Chaumontet¹,

Suschetet

Honikman-Leban

et al. 1996

Nutrition and Cancer

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Possible tumor-promoting activity of four flavonoids, quercetin (QC), tangeretin (TG), flavone (FO), and flavanone (FN), was examined in a rat liver short-term carcinogenesis assay as well as with in vivo and in vitro assays of inhibition of gap junctional intercellular communication (GJIC). Rat hepatocarcinogenesis was induced by aflatoxin B1 treatment followed by a selection phase (2-acetylaminofluorene treatment and partial hepatectomy), then treatment with or without test chemicals (in vivo studies of antipromotion were not performed). Using glutathione S-transferase placental form (GST-P)-positive foci, we compared the effects of flavonoids (at 1,000 ppm in the diet) with the effects of phenobarbital (PB) on the occurrence of liver preneoplastic lesions. In addition, we studied the effects of flavonoids on GJIC in the livers derived from these experiments and in two types of cultured cells. No significant difference in the number and area of GST-P-positive foci was found after one or three months of treatment between any flavonoid group and control group. In the positive control group, PB markedly increased the numbers and areas of preneoplastic lesions at three months. Whereas PB also decreased by 60% the average size of lucifer yellow dye spread in slices of liver parenchyma free of preneoplastic lesions among the different flavonoids, only TG decreased the dye transfer in vivo: by 30% at one month and 50% at three months. With the dye transfer assay applied to a rat liver epithelial cell line (REL) and the Chinese hamster V79 metabolic cooperation assay, none of the tested flavonoids (< or = 25 microM) inhibited GJIC. Conversely, protective properties were seen for some of the compounds in antipromotion in vitro studies, because TG and FN enhanced the dye transfer in REL cells and FO, TG, and QC partly prevented the inhibition of metabolic cooperation by 12-O-tetradecanoylphorbol-13-acetate. Thus, taken together, our results suggest that QC, FO, and FN do not show tumor-promoting activity. Concerning TG, some discrepancies in the in vivo data are observed. Some of them (GJIC inhibition in liver slices) are probably more relevant to promotion of hepatocarcinogenesis.

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Studies on the Modulating Effects of Retinoic Acid and Retinol Acetate Using Dye Transfer and Metabolic Cooperation Assays

Cited by 5 publications

References 0 publications

Hormesis: Why it is Important to Toxicology and Toxicologists

Hormesis: Why it is Important to Toxicology and Toxicologists

Retinoic acid enhances connexin43 expression at the post‐transcriptional level in rat liver epithelial cells

Lack of tumor‐promoting effects of flavonoids: Studies on rat liver preneoplastic foci and onin vivoandin vitrogap junctional intercellular communication

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