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Inhibition of intercellular communication: An in vitro assay for detecting potential tumour promoters
1FRAME Alternatives Laboratory, Department of Human Morphology, University of Nottingham Medical School, Nottingham NG7 2UH, UK.
Abstract:
The effects of non-cytotoxic concentrations of 13 chemicals on gap junctional intercellular communication (GJIC) in human keratinocytes and WB 344 cells were determined using a scrape-labelling method. The chemicals were selected according to their reported tumour-promoting effects in either the skin or liver, or their known skin irritancy potential. The in vitro assay was able to discriminate between genotoxic and non-genotoxic chemicals and, with keratinocyte cultures, ranked correctly a series of phorbol esters with regard to their reported tumour-promoting potencies in vivo. The data obtained support the suggestion that measurement of the inhibition of GJIC in vitro may provide a means to distinguish substances that have different tumour-promoting potencies.
Insights
This study shows that measuring inhibition of gap junctional intercellular communication (GJIC) in vitro can help distinguish chemicals with different tumor-promoting effects. This assay effectively ranked phorbol esters by potency.
Area of Science:
- Toxicology
- Cell Biology
- Carcinogenesis
Background:
- Gap junctional intercellular communication (GJIC) plays a crucial role in cellular regulation.
- Tumor promoters are agents that enhance the development of cancer but do not initiate it.
- Assessing tumor-promoting potential is vital for chemical safety evaluation.
Purpose of the Study:
- To evaluate the effects of non-cytotoxic concentrations of 13 tumor promoters and irritants on GJIC.
- To determine if in vitro GJIC inhibition assays can predict in vivo tumor-promoting potencies.
- To assess the assay's ability to differentiate genotoxic from non-genotoxic chemicals.
Main Methods:
- Utilized a scrape-labelling method to measure GJIC in human keratinocytes and WB 344 cells.
- Selected 13 chemicals based on known tumor-promoting effects (skin/liver) or skin irritancy.
- Exposed cells to non-cytotoxic concentrations of selected chemicals.
Main Results:
- The in vitro assay successfully discriminated between genotoxic and non-genotoxic chemicals.
- Keratinocyte cultures accurately ranked phorbol esters according to their known in vivo tumor-promoting potencies.
- Significant inhibition of GJIC was observed for several tested chemicals.
Conclusions:
- Measurement of GJIC inhibition in vitro is a promising method for distinguishing chemicals with varying tumor-promoting potencies.
- This assay can serve as a valuable tool in the toxicological assessment of chemicals.
- The findings support the use of GJIC assays for predicting in vivo carcinogenic potential.
