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DNA breakage of human leukemia cells by clomiphene, an ovulation-inducing agent
Biochemical and Biophysical Research Communications
|August 14, 1986
Summary
Clomiphene citrate, an ovulation drug, significantly increases poly(ADP-ribose) synthesis in lymphoblastic leukemia cells, indicating DNA damage. This DNA damage likely inhibits cell growth, suggesting a potential new therapeutic avenue.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Poly(ADP-ribose) synthesis is a cellular response to DNA damage.
- Clomiphene citrate is an ovulation-inducing agent with potential cytotoxic effects.
Purpose of the Study:
- To investigate the effect of clomiphene citrate on poly(ADP-ribose) synthesis in HPB-ALL cells.
- To determine if clomiphene citrate induces DNA damage in these cells.
- To correlate DNA damage with cell growth inhibition.
Main Methods:
- Treatment of HPB-ALL cells with clomiphene citrate.
- Measurement of poly(ADP-ribose) synthesizing activity.
- Alkaline sucrose density gradient centrifugation to detect DNA strand breaks.
- Cell growth inhibition assays.
Main Results:
- Clomiphene citrate increased poly(ADP-ribose) synthesis up to 4-fold in HPB-ALL cells.
- Increased single-strand DNA breaks were observed with increasing clomiphene citrate concentrations.
- Clomiphene citrate inhibited cell growth with an IC50 of 5 micrograms/ml.
Conclusions:
- Clomiphene citrate induces DNA damage in human lymphoblastic leukemia cells.
- The DNA-damaging effect of clomiphene citrate contributes to its observed inhibition of cell growth.
- Unlike bleomycin, clomiphene citrate did not directly activate purified poly(ADP-ribose) synthetase in vitro.