Related Experiment Videos
ATP-resistant variants of transformed mouse fibroblasts
1Department of Microbiology, George S. Wise Faculty of Life Sciences Tel Aviv University, Israel.
Abstract:
Addition of ATP to cultures of transformed mouse fibroblasts, 3T6 cells, resulted in cell growth inhibition, whereas the growth of the non-transformed counterparts, 3T3 cells, was only slightly affected. The inhibition was found to be specific for adenine nucleotides, and concentration dependent. At relatively low concentrations (e.g., 1.0 mM) the effect of ATP was cytostatic, whereas at higher concentrations (e.g., 1.0 mM) a cytotoxic effect was exerted. ATP-resistant variants of 3T6 cells were selected by exposure of cultures to gradually elevated concentrations of ATP. The variants were found to resemble the non-transformed counterparts, 3T3 cells, more than the 3T6 parent cells, by the following criteria: ATP-induced alterations in the membrane potential, changes in membrane permeability, cell growth inhibition, and colony formation on soft agar. The data indicate that long exposure of the transformed cells to external ATP results in redifferentiation and reduction in their tumorigenicity.
Insights
Adenosine triphosphate (ATP) inhibits transformed mouse 3T6 cell growth, unlike non-transformed 3T3 cells. ATP-resistant variants exhibit reduced tumorigenicity, suggesting redifferentiation.
Area of Science:
- Cell biology
- Biochemistry
- Cancer research
Background:
- Transformed cells, such as 3T6 mouse fibroblasts, exhibit uncontrolled growth.
- Non-transformed cells, like 3T3 mouse fibroblasts, have regulated growth patterns.
- External adenosine triphosphate (ATP) effects on cell transformation are not fully understood.
Purpose of the Study:
- To investigate the impact of exogenous ATP on the growth and characteristics of transformed and non-transformed mouse fibroblasts.
- To determine if ATP exposure can reverse transformed cell phenotypes and reduce tumorigenicity.
Main Methods:
- Culturing of 3T6 (transformed) and 3T3 (non-transformed) mouse fibroblasts.
- Treatment with varying concentrations of ATP.
- Selection of ATP-resistant 3T6 variants.
- Assessment of cell growth, membrane potential, membrane permeability, and soft agar colony formation.
Main Results:
- ATP specifically inhibited 3T6 cell growth in a dose-dependent manner, with cytostatic effects at lower concentrations and cytotoxic effects at higher concentrations.
- 3T3 cell growth was only slightly affected by ATP.
- ATP-resistant 3T6 variants displayed characteristics similar to 3T3 cells, including altered membrane potential and permeability, reduced growth inhibition, and decreased soft agar colony formation.
- Long-term ATP exposure led to redifferentiation and reduced tumorigenicity in 3T6 cells.
Conclusions:
- External ATP can selectively inhibit transformed cell growth and induce phenotypic reversion.
- ATP-induced redifferentiation in transformed cells is associated with reduced tumorigenicity.
- ATP may serve as a potential therapeutic agent for targeting cancer cells.