Giri A K, Lu L J
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1110, USA.
Cancer Lett. 1995 Aug 16;95(1-2):125-33. doi: 10.1016/0304-3835(95)03877-y.
Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells. DMBA alone induced 11.73 +/- 1.42 SCE/cell compared to 4.35 +/- 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20% fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 x 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20%. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34%, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.
食用大豆的人群患乳腺癌、结肠癌和前列腺癌的几率降低，这可能部分归因于大豆中存在的两种具有雌激素活性的异黄酮——染料木黄酮和大豆苷元。本研究调查了这些大豆异黄酮的遗传毒性，以及它们与7,12 - 二甲基苯并[a]蒽（DMBA）诱导的小鼠骨髓细胞姐妹染色单体交换（SCE）和肝脏及乳腺中DNA加合物形成的相互作用。将雌性ICR小鼠分组，腹腔注射大豆苷元或/和染料木黄酮（每天10 - 20 mg/kg，共6天，或每12小时50 mg/kg，共3天），或注射溶剂二甲基亚砜（DMSO）进行预处理。小鼠皮下植入溴脱氧尿苷（BrdU）片剂，并分别在处死前24、23和2小时腹腔注射DMBA（50 mg/kg）和秋水仙碱（4 mg/kg）。在骨髓细胞中，单独使用DMBA诱导的SCE为11.73±1.42个/细胞，而DMSO处理的对照组为4.35±0.83个/细胞（P = 0.001）。与未进行预处理的小鼠相比，用大豆苷元、染料木黄酮或染料木黄酮与大豆苷元组合（每天6×20 mg/kg，共6天）预处理的小鼠，DMBA诱导的SCE减少了20%（P < 0.05）。每12小时50 mg/kg，共3天的染料木黄酮处理也使DMBA诱导的SCE减少了20%。然而，单独用每12小时50 mg/kg的染料木黄酮或大豆苷元处理3天，或大豆苷元加染料木黄酮组合处理（不进行DMBA处理），也比仅用溶剂（DMSO）处理诱导了更多的SCE（P < 0.05）。与用DMSO预处理相比，用低剂量和高剂量的大豆苷元加染料木黄酮或高剂量的染料木黄酮预处理会降低骨髓细胞的复制指数（P < 0.05）。用染料木黄酮预处理可使DMBA诱导的DNA加合物形成减少34%，但由于加合物水平存在较大的个体间差异，这一结果仅具有边缘显著性（P = 0.08）。这些结果表明，染料木黄酮和大豆苷元可抑制已知致癌物DMBA诱导的SCE，并可能抑制DNA加合物的形成。这种对低剂量异黄酮暴露的反应可能部分解释了食用大豆对内分泌癌的保护作用。
