Related Experiment Videos
Effects of selected anti-tumor-promoting chemicals on metabolic cooperation between Chinese hamster V79 cells
L J Mills1, S M Nelson, A R Malcolm
1Science Applications International Corporation, U.S. Environmental Protection Agency, Narragansett, Rhode Island 02882.
Abstract:
Many tumor-promoting chemicals inhibit gap junctional communication between cells. We investigated the possibility that antipromoting chemicals may act inversely and enhance gap junctional communication. The V79/metabolic cooperation assay is an in vitro test that measures gap junctional communication indirectly by determining the extent of metabolic cooperation between mutant and wild-type V79 Chinese hamster lung fibroblasts in culture. Six in vivo antipromoters (caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenylalanine chloromethyl ketone (TPCK), and acetic acid) were tested in this assay to assess their effects on metabolic cooperation. Caffeine, IBMX, phenidone, and dibromoacetophenone had no effect on metabolic cooperation, while TPCK slightly inhibited metabolic cooperation in one V79 assay. Acetic acid appeared to facilitate metabolic cooperation. In tests where an antipromoter was combined with the established tumor promoter phorbol 12-myristate 13-acetate (PMA), acetic acid, caffeine, and IBMX counteracted PMA-induced inhibition of metabolic cooperation, while phenidone, dibromoacetophenone, and TPCK had little effect. These results indicate that some antipromoters interfere with the ability of a tumor-promoting chemical to inhibit metabolic cooperation and suggest that alteration of gap junctional communication can be a mechanism of antipromoter action.
Insights
Some chemicals that prevent tumors may enhance cell communication, counteracting tumor promoters. Acetic acid and caffeine showed potential in this study by restoring inhibited gap junctional communication.
Area of Science:
- Cell Biology
- Cancer Research
- Pharmacology
Background:
- Tumor-promoting chemicals are known to inhibit gap junctional communication (GJC) between cells.
- The inverse relationship between tumor promotion and GJC suggests antipromoters might enhance GJC.
Purpose of the Study:
- To investigate if antipromoting chemicals can enhance GJC.
- To assess the effects of six in vivo antipromoters on metabolic cooperation, an indicator of GJC.
Main Methods:
- Utilized the V79/metabolic cooperation assay, an in vitro method measuring GJC indirectly.
- Tested six antipromoters: caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenylalanine chloromethyl ketone (TPCK), and acetic acid.
- Evaluated the effects of antipromoters alone and in combination with phorbol 12-myristate 13-acetate (PMA), a tumor promoter.
Main Results:
- Acetic acid facilitated metabolic cooperation, while TPCK slightly inhibited it.
- Caffeine, IBMX, phenidone, and dibromoacetophenone showed no significant effect on metabolic cooperation.
- Acetic acid, caffeine, and IBMX counteracted the inhibitory effect of PMA on metabolic cooperation.
Conclusions:
- Some antipromoters can interfere with tumor promoters' ability to inhibit GJC.
- Alteration of GJC is a potential mechanism underlying the action of certain antipromoters.
- Acetic acid and caffeine show promise as agents that can modulate GJC in the context of tumor promotion.