Gossypol-induced DNA breaks in rat lymphocytes are secondary to cytotoxicity.
Gossypol, a male antifertility and potential anticancer agent, was found to induce DNA strand breaks in rat lymphocytes. DNA breaks were measured with the single-cell gel electrophoresis (SCGE) or 'comet' assay. A significant increase in DNA breaks was observed after 1 h incubation at concentrations of 2 microg/ml or greater. The inclusion of 10% fetal bovine serum in the media reduced the toxicity of gossypol, and DNA breaks were only observed at a concentration of 80 microg/ml. However, the increase in DNA strand breaks, for incubations with and without serum, only occurred when cell viability was reduced to less than 70%. Examination of cell morphology and DNA fragmentation at incubations up to 5 h yielded no evidence that DNA strand breaks were occurring due to apoptosis. We conclude that gossypol is not primarily genotoxic in this cell type, and that the DNA breaks observed arose secondary to cytotoxicity.
Quintana
P J
PJ
Division of Occupational and Environmental Health, Graduate School of Public Health, San Diego State University, 5500 Campanile Dr. HT-119, San Diego, CA 92182-4162, USA. jquintan@mail.sdsu.edu
de Peyster
A
A
Klatzke
S
S
Park
H J
HJ
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006072:Gossypol / Q000633:toxicity*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003470:Culture Media; D016895:Culture Media, Serum-Free; D006072:Gossypol