Zsivkovits Markus, Fekadu Kassie, Sontag Gerhard, Nabinger Ursula, Huber Wolfgang W, Kundi Michael, Chakraborty Asima, Foissy Helmuth, Knasmüller Siegfried
Institute of Cancer Research, Borschkegasse 8a, A-1090 Vienna, Austria.
Carcinogenesis. 2003 Dec;24(12):1913-8. doi: 10.1093/carcin/bgg167. Epub 2003 Sep 11.
The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef ('beef mix') and chicken ('chicken mix'). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with a high consumption of LB-containing foods.
本研究的目的是调查用于生产酸奶的四种不同乳酸菌(LB)菌株,即保加利亚乳杆菌291、嗜热链球菌F4、嗜热链球菌V3和长双歧杆菌BB536,对杂环芳香胺(HCA)的DNA损伤作用的影响。将雄性F344大鼠口服含有2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶、2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉、2-氨基-3,4,8-三甲基-3H-咪唑并[4,5-f]喹喔啉、2-氨基-9H-吡啶并[2,3-b]吲哚和2-氨基-3-甲基-3H-咪唑并[4,5-f]喹啉的HCA混合物,这些是在煎牛肉(“牛肉混合物”)和鸡肉(“鸡肉混合物”)中发现的HCA含量的代表。在给予HCA之前和不同时间段,通过灌胃给动物给予LB悬浮液。随后,在单细胞凝胶电泳(SCGE)试验中测量结肠和肝细胞中的DNA迁移程度。在给予1×10¹⁰个LB细胞/动物后,所有四种菌株均完全抑制了牛肉混合物诱导的DNA损伤,而对于鸡肉混合物,仅观察到轻微(无统计学意义)的影响。牛肉诱导的DNA损伤的抑制呈剂量依赖性,当给予1×10⁷个细胞/动物时仍具有统计学意义。动力学研究表明,当在牛肉混合物之前12小时给予LB时,保护作用仍然显著。将本研究结果与体外实验的化学分析数据进行比较表明,在动物中观察到的DNA迁移的强烈减少只能部分由直接结合作用来解释。本研究结果表明,在与人类相关的条件下,LB对HCA的遗传毒性作用具有高度保护作用,并为一些粪便中LB计数高或食用含LB食物量高的个体的结肠癌发病率降低的观察结果提供了一种可能的解释。