Martino P E, Diaz Gomez M I, Tamayo D, Lopez A J, Castro J A
Cátedra de Patologia de Aves Piliferos, Facultad de Ciencias Veterinarias, Universidad de La Plata, Buenos Aires, Argentina.
J Toxicol Environ Health. 1988;23(2):183-92. doi: 10.1080/15287398809531105.
Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. We have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared them with those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N7-methylguanine and O6-methylguanine adducts. Biotransformation of NDMA by liver slices to CO2 was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also to a higher intrinsic susceptibility of their liver cells to a given chemical insult.
在阿根廷的一个水貂养殖群落中检测到肝坏死和肝血管肉瘤的爆发。对水貂食物的分析显示其中含有2.6 ppm的二甲基亚硝胺（NDMA），显然这是添加亚硝酸盐作为防腐剂的结果。先前的研究证明了水貂对NDMA和其他肝脏损伤具有特殊的易感性。我们测定了几个已知与NDMA肝毒性作用相关的生化参数，并将它们与大鼠肝脏中的参数进行了比较。给这两个物种施用NDMA均导致形成能够与肝脏DNA相互作用以产生N7-甲基鸟嘌呤和O6-甲基鸟嘌呤加合物的反应性代谢产物。水貂肝脏切片将NDMA生物转化为二氧化碳的能力明显低于大鼠，而与核酸的共价结合（CB）略低于大鼠。水貂中氨基比林N-脱甲基酶活性也明显低于大鼠肝脏。与大鼠相比，水貂中NDMA反应性代谢产物与微粒体蛋白的CB没有显著降低，微粒体制剂将NDMA生物转化为甲醛的情况也是如此。结果表明，水貂对NDMA的高易感性可能部分归因于其解毒NDMA能力的下降，但也归因于其肝细胞对特定化学损伤的更高内在易感性。
