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Published on: November 10, 2013
[Effect of the antitumor antibiotic actinoxanthine on cells cultured in vitro]
Abstract:
Significant changes in the nucleus structure, complete suppression of the mitotic activity, markedly decreased synthesis of RNA (by 70--80 per cent according to incorporation of 3H-uridine) and decreased levels of DNA (by 40 per cent according to olivomycin binding) were observed in the fibroblasts cultivated in vitro due to exposure to actinoxanthine in an amount of 50 microgram/ml. The data indicate direct damaging effect of the drug on the cell chromatin. The above nuclear changes were also observed after a short-term exposure of the cells to the drug (up to 5 minutes). Still, they became evident only after the subsequent incubation of the cells in a pure culture medium for at least 15 minutes. No such changes in the nucleus structure were detected when after the 5-minute exposure to actinoxanthine the cells were exposed to trypsin for 3 minutes. When the time of exposure to actinoxanthine was longer (15 minutes and higher), trypsin suppressed the manifestation of the above nuclear changes. The two-stage mechanism of the damaging effect of actinoxanthine on the chromatin of the cells cultivated in vitro is discussed. The damaging effect of actinoxanthine on the cells begins from binding of the drug with the cell membrane. After that a short incubation period follows and then the characteristic changes in the nucleus structure appear.
Insights
Actinoxanthine directly damages fibroblast cell chromatin, significantly reducing RNA and DNA synthesis and altering nuclear structure. These effects manifest after a brief incubation period, indicating a two-stage cellular response.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Actinoxanthine is a compound investigated for its cellular effects.
- Understanding the mechanism of action of cytotoxic agents is crucial in cell biology.
Purpose of the Study:
- To investigate the effects of actinoxanthine on fibroblast cell structure and function.
- To elucidate the mechanism and timeline of actinoxanthine-induced cellular damage.
Main Methods:
- Fibroblast cell cultures were exposed to actinoxanthine (50 microgram/ml).
- RNA synthesis was measured using 3H-uridine incorporation.
- DNA levels were assessed via olivomycin binding.
- Cellular responses were observed after varying exposure and incubation times, including with trypsin treatment.
Main Results:
- Actinoxanthine caused significant nuclear structure changes, suppressed mitotic activity, and decreased RNA synthesis (70-80%) and DNA levels (40%).
- These effects were observed even after short exposures (up to 5 minutes) but became evident after 15 minutes of post-exposure incubation.
- Trypsin treatment inhibited the manifestation of nuclear changes, particularly with longer actinoxanthine exposure times.
Conclusions:
- Actinoxanthine exerts a direct damaging effect on cell chromatin.
- A two-stage mechanism is proposed, initiated by actinoxanthine binding to the cell membrane, followed by incubation and subsequent nuclear alterations.
- The findings highlight the complex interaction of actinoxanthine with cellular components.
