DNA breakage of human leukemia cells by clomiphene, an ovulation-inducing agent.
When HPB-ALL, human lymphoblastic leukemia cells were treated with clomiphene citrate, an ovulation-inducing agent, poly(ADP-ribose) synthesizing activity of the cells increased up to 4 fold. This stimulatory effect was almost comparable to that of bleomycin, a typical DNA strand breaking agent. Since the agents causing DNA breakage stimulate poly(ADP-ribose) synthesis in cells [Berger, N. A., Sikorski, G. W., Petzold, S. J., and Kurohara, K. K. J. Clin. Invest. 63, 1164-1171 (1979)], clomiphene citrate is suggested to damage DNA of the cells. In fact, an increase of single strand breakage of the DNA was detected by using alkaline sucrose density gradient centrifugation when the HPB-ALL cells were treated with increasing concentration of clomiphene. The inhibition of the cell growth by clomiphene citrate (IC50 = 5 micrograms/ml) appeared to be ascribable to its potent DNA-damaging effect. Although bleomycin activated purified poly(ADP-ribose) synthetase by cleaving covalently closed circular plasmid pBR322 DNA in vitro, clomiphene citrate per se did not.
D001761:Bleomycin / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002996:Clomiphene / Q000633:toxicity*; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007945:Leukemia, Lymphoid; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D010957:Plasmids; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
D009702:Nucleoside Diphosphate Sugars; D001761:Bleomycin; D002996:Clomiphene; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases