Quintana P J, de Peyster A, Klatzke S, Park H J
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.
Toxicol Lett. 2000 Sep 30;117(1-2):85-94. doi: 10.1016/s0378-4274(00)00244-7.
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.
棉酚是一种男性抗生育剂及潜在的抗癌剂，已发现它能诱导大鼠淋巴细胞中的DNA链断裂。DNA断裂通过单细胞凝胶电泳（SCGE）或“彗星”试验进行测定。在浓度为2微克/毫升或更高时，孵育1小时后观察到DNA断裂显著增加。培养基中加入10%胎牛血清可降低棉酚的毒性，仅在浓度为80微克/毫升时观察到DNA断裂。然而，无论有无血清孵育，只有当细胞活力降低到70%以下时，DNA链断裂才会增加。在长达5小时的孵育过程中检查细胞形态和DNA片段化，没有证据表明DNA链断裂是由凋亡引起的。我们得出结论，棉酚在这种细胞类型中并非主要具有基因毒性，观察到的DNA断裂是细胞毒性的继发结果。
