Related Experiment Video
Updated: Aug 5, 2026
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
Inhibition of DNA synthesis in mouse lymphosarcoma LS/BL cells by fluorocitrate
Abstract:
Fluorocitrate is a specific inhibitor of aconitase activity (EC 4.2.1.3). It causes an inhibition of citric acid cycle reactions and consequently reduces the oxygen consumption, as well as the total volume of oxidative phosphorylations. Experiments using 3H-thymidine incorporation into mouse lymphosarcoma LS/BL cells proved that the in vitro blocking of citric acid cycle by fluorocitrate (3.6 and 7.2 mM) was accompanied by a decrease in DNA synthesis by 40 to 60 percent, as compared to control cells. A similar inhibitory effect upon DNA synthesis was also found in cells cultured in the abdominal cavity of host mice injected intraperitoneally with 5 mg./kg. of sodium fluoroacetate. Following the injection, fluorocitrate is formed in vivo by way of Peters' lethal synthesis.
Insights
Fluorocitrate inhibits the citric acid cycle, reducing cellular respiration and DNA synthesis. This specific aconitase inhibitor impacts both in vitro and in vivo cancer cell proliferation.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Fluorocitrate is a known inhibitor of aconitase (EC 4.2.1.3).
- Aconitase inhibition disrupts the citric acid cycle, affecting cellular energy production.
- The citric acid cycle is crucial for cellular respiration and metabolic processes.
Purpose of the Study:
- To investigate the effect of fluorocitrate on DNA synthesis in cancer cells.
- To determine if fluorocitrate, formed in vivo, impacts DNA synthesis.
- To elucidate the role of aconitase inhibition in cellular proliferation.
Main Methods:
- In vitro experiments using 3H-thymidine incorporation to measure DNA synthesis in mouse lymphosarcoma LS/BL cells.
- Exposure of cells to varying concentrations of fluorocitrate (3.6 and 7.2 mM).
- In vivo studies involving intraperitoneal injection of sodium fluoroacetate into host mice, followed by analysis of tumor cells.
Main Results:
- In vitro exposure to fluorocitrate significantly decreased DNA synthesis by 40-60% compared to controls.
- In vivo formation of fluorocitrate via Peters' lethal synthesis led to a similar inhibition of DNA synthesis in tumor cells.
- Fluorocitrate effectively blocked citric acid cycle reactions, reducing oxygen consumption and oxidative phosphorylation.
Conclusions:
- Fluorocitrate is a potent inhibitor of DNA synthesis in cancer cells.
- Inhibition of the citric acid cycle by fluorocitrate has significant implications for cellular metabolism and proliferation.
- Targeting aconitase activity represents a potential strategy for cancer therapy.
