Josyula S, Schut H A
Department of Pathology, Medical College of Ohio, Toledo 43699, USA.
Food Chem Toxicol. 1999 Apr;37(4):287-96. doi: 10.1016/s0278-6915(99)00018-6.
The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is carcinogenic in the CDF1 mouse, causing lymphomas (spleen and lymph nodes) and in the F344 rat, causing mammary tumours in the female and colon tumours in the male. Dietary fish oil, a rich source of omega-3 fatty acids, exhibits chemopreventive properties in several rodent tumour models. The potential chemopreventive properties of dietary omega-3 fatty acid ethyl ester concentrate (O3C) were tested by evaluating its effects on the formation and removal of PhIP-DNA adducts. In the first experiment, a powdered AIN-76A diet containing 4.0% (w/w) O3C inhibited PhIP-DNA adduct formation in various organs of the CDF1 mouse, but not in those of the F344 rat. In a subsequent, second experiment, groups of male CDF1 mice were maintained for 43 days on AIN-76A diets containing the following percentages (w/w) of corn oil ethyl esters and O3C: 7.0 and 0, 5.5 and 1.5, 4.0 and 3.0, and 1.0 and 6.0, respectively. All animals received 0.04% (w/w) PhIP in the diet during weeks 3 and 4. Using 32P-postlabelling assays, PhIP-DNA adducts were analysed in various organs and white blood cells (WBC) on days 1, 8 and 15 after removal of PhIP from the diet. In the liver, O3C-containing diets inhibited adduct formation at all three time points (40.3-60.0%, 53.4-75.7% and 43.3-64.3% on days 1, 8 and 15, respectively). In the spleen, inhibition was evident only on days 8 (35.4-38.8%) and 15 (38.4-56.5%). O3C diets inhibited adduct formation in the stomach, small intestine and caecum at all three time points (except in the stomach and caecum on day 15) amounting to 18.5-31.5% decreases in the stomach, 40.0-60.3% decreases in the small intestine and 24.4-31.4% decreases in the caecum. The extent of inhibition was not related to O3C concentration. In the colon and WBC, adduct levels were independent of the type of diet. In all organs, adduct levels decreased significantly over time, with day 15 levels being 6.3-31.6% of those on day 1. Rate of adduct removal was independent of the type of diet. It is concluded that dietary O3C inhibits PhIP-DNA adduct formation in a target organ (spleen) as well as in non-target organs (liver and gastrointestinal tract) of the CDF1 mouse, but that the rate of adduct removal is independent of the O3C content of the diet.
杂环胺2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）对CDF1小鼠具有致癌性，可引发淋巴瘤（脾脏和淋巴结），对F344大鼠也有致癌性，可使雌性大鼠患乳腺肿瘤，雄性大鼠患结肠肿瘤。膳食鱼油是ω-3脂肪酸的丰富来源，在几种啮齿动物肿瘤模型中具有化学预防特性。通过评估膳食ω-3脂肪酸乙酯浓缩物（O3C）对PhIP-DNA加合物形成和清除的影响，测试了其潜在的化学预防特性。在第一个实验中，含有4.0%（w/w）O3C的粉状AIN-76A日粮抑制了CDF1小鼠各器官中PhIP-DNA加合物的形成，但对F344大鼠的器官没有抑制作用。在随后的第二个实验中，将雄性CDF1小鼠分组，分别用含有以下百分比（w/w）玉米油乙酯和O3C的AIN-76A日粮饲养43天：7.0和0、5.5和1.5、4.0和3.0以及1.0和6.0。在第3周和第4周期间，所有动物的日粮中均含有0.04%（w/w）的PhIP。在从日粮中去除PhIP后的第1天、第8天和第15天，使用32P后标记分析法对各器官和白细胞（WBC）中的PhIP-DNA加合物进行分析。在肝脏中，含O3C的日粮在所有三个时间点均抑制了加合物的形成（第1天、第8天和第15天分别为40.3 - 60.0%、53.4 - 75.7%和43.3 - 64.3%）。在脾脏中，仅在第8天（35.4 - 38.8%）和第15天（38.4 - 56.5%）有明显抑制作用。O3C日粮在所有三个时间点均抑制了胃、小肠和盲肠中加合物的形成（第15天的胃和盲肠除外），胃中加合物减少了18.5 - 31.5%，小肠中减少了40.0 - 60.3%，盲肠中减少了24.4 - 31.4%。抑制程度与O3C浓度无关。在结肠和白细胞中，加合物水平与日粮类型无关。在所有器官中，加合物水平随时间显著下降，第15天的水平为第1天的6.3 - 31.6%。加合物清除率与日粮类型无关。结论是，膳食O3C可抑制CDF1小鼠靶器官（脾脏）以及非靶器官（肝脏和胃肠道）中PhIP-DNA加合物的形成，但加合物的清除率与日粮中的O3C含量无关。
