Khan Tajdar Husain, Prasad Lakshmi, Sultana Sarwat
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Hum Exp Toxicol. 2005 Mar;24(3):149-55. doi: 10.1191/0960327105ht504oa.
Dietary factors are considered important environmental risk determinants for various diseases. Isoflavones are one of the biologically active polyphenolic plant constituents that possess potential chemopreventive properties against a wide variety of chronic diseases. In the present study we have evaluated the antimutagenic potential of soy isoflavones against benzo(a)pyrene (B[a]P) (125 mg/ kg) induced genotoxicity in Swiss albino mice. The effect of soy isoflavones was studied by in vivo bone marrow chromosomal aberration and micronuclei induction test. Using an alkaline unwinding assay we monitored the DNA strand breaks. Two doses of soy isoflavones (20 and 40 mg/kg b.wt) were given orally for seven days prior to the administration of B[a]P. Soy isoflavone inhibited the genotoxicity of B[a]P in terms of chromosomal aberration and micronucleus formation. DNA strand break levels in only B[a]P treated group remained significantly high from the control values (P < 0.001). The pretreatment of soy isoflavone showed gradual reduction in strand breaks significantly (P < 0.001) and dose dependently. Soy isoflavone pretreatment also decreased cytochrome P450 (CYP) content. The activity of CYP was also decreased dose dependently by pretreatment with soy isoflavone. The chemopreventive effect of soy isoflavone on the inhibition of CYP activity and DNA integrity mediate the possible mechanism of inhibition of genotoxicity.
饮食因素被认为是多种疾病重要的环境风险决定因素。异黄酮是具有生物活性的多酚类植物成分之一，对多种慢性疾病具有潜在的化学预防特性。在本研究中，我们评估了大豆异黄酮对苯并(a)芘（B[a]P，125毫克/千克）诱导的瑞士白化小鼠遗传毒性的抗诱变潜力。通过体内骨髓染色体畸变和微核诱导试验研究了大豆异黄酮的作用。使用碱性解旋测定法监测DNA链断裂情况。在给予B[a]P之前，口服两种剂量的大豆异黄酮（20和40毫克/千克体重），持续7天。大豆异黄酮在染色体畸变和微核形成方面抑制了B[a]P的遗传毒性。仅B[a]P处理组的DNA链断裂水平与对照组相比仍显著较高（P < 0.001）。大豆异黄酮预处理显示链断裂明显逐渐减少（P < 0.001）且呈剂量依赖性。大豆异黄酮预处理还降低了细胞色素P450（CYP）含量。大豆异黄酮预处理也使CYP活性呈剂量依赖性降低。大豆异黄酮对CYP活性抑制和DNA完整性的化学预防作用介导了抑制遗传毒性的可能机制。
