大鼠对小剂量口服二甲基亚硝胺的吸收与代谢。对二甲基亚硝胺在人类食物中可能存在的危害的启示。

The absorption and metabolism in rats of small oral doses of dimethylnitrosamine. Implication for the possible hazard of dimethylnitrosamine in human food.

Gomez M I, Swann P F, Magee P N

Biochem J. 1977 Jun 15;164(3):497-500. doi: 10.1042/bj1640497.

Abstract

Groups of rats were given one dose of the carcinogen dimethylnitrosamine by gastric intubation. The dose was varied between 10mg/kg body wt. and 1 microgram/kg body wt. 2. The dose was rapidly absorbed. 3. The methylation of liver DNA resulting from the administration of this carcinogen was proportional to dose. This suggests that small doses are absorbed from the gut with no more loss than large doses. 4. As the dose was decreased there was a disproportionately greater decrease in the alkylation of kidney DNA, and when the dose was less than 40 microgram/kg body wt. the methylation of kidney DNA was no longer detectable. This possibly explains why small amounts of dimethylnitrosamine in the diet do not induce kidney tumours. 5. Comparison of the relative alkylation of liver DNA and kidney DNA resulting from an oral and from an intravenous dose of dimethylnitrosamine suggest that small amounts of dimethylnitrosamine absorbed into the portal blood from the gut are completely metabolized by the liver and do not enter the general circulation. 6. The implications of these results for the possible hazard of dimethylnitrosamine in human food is discussed.

摘要

通过胃管给大鼠群体一次性给予致癌物质二甲基亚硝胺。剂量在10毫克/千克体重至1微克/千克体重之间变化。2. 该剂量迅速被吸收。3. 给予这种致癌物质后肝脏DNA的甲基化与剂量成正比。这表明小剂量从肠道吸收时的损失并不比大剂量更多。4. 随着剂量降低，肾脏DNA的烷基化下降幅度不成比例地更大，当剂量小于40微克/千克体重时，肾脏DNA的甲基化不再能检测到。这可能解释了为什么饮食中少量的二甲基亚硝胺不会诱发肾脏肿瘤。5. 口服和静脉注射二甲基亚硝胺后肝脏DNA和肾脏DNA相对烷基化的比较表明，从肠道吸收进入门静脉血的少量二甲基亚硝胺被肝脏完全代谢，不会进入体循环。6. 讨论了这些结果对人类食物中二甲基亚硝胺可能危害意味着什么。