Pool B L, Brendler S, Klein R G, Monarca S, Pasquini R, Schmezer P, Zeller W J
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Carcinogenesis. 1988 Jul;9(7):1247-52. doi: 10.1093/carcin/9.7.1247.
Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single-strand breaks induced by N-nitroso-acetoxymethylmethylamine, N-nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung. Blood serum enzyme levels were not greatly different from each other, except for lactate dehydrogenase which was elevated in SO2-exposed animals.
进行了短期体内研究，以研究常见空气污染物二氧化硫（SO₂）或氮氧化物（NOₓ）的生物学效应及其对亚硝胺遗传毒性活性的影响。从吸入50 ppm SO₂或NOₓ达2周的斯普拉格-道利大鼠中分离出肝细胞和肺细胞。将细胞孵育1小时后，通过测量由N-亚硝基-乙酰氧基甲基甲胺、N-亚硝基二甲胺和N-亚硝基甲基苄胺诱导的DNA单链断裂来测定肝细胞中的遗传毒性。在孵育1小时后，还测定了肝和肺细胞中的毒性参数（台盼蓝排斥法和血清酶泄漏）。在从肺和肝组织分离的亚细胞微粒体组分中测定芳烃羟化酶（AHH）、亚硝基二甲胺脱甲基酶（NDMA-D）和谷胱甘肽-S-转移酶（GST）的活性。最后，作为总体毒性的指标，测定了大鼠血清中各种血清酶的活性。结果发现，三种亚硝胺诱导的DNA单链断裂在经SO₂处理动物的肝细胞中有所减少。通过台盼蓝排斥法测定，大鼠肝细胞和大鼠肺细胞的活力在所有三个处理组中，在刚分离后以及与二甲基亚砜（DMSO）或亚硝胺孵育1小时后均相似。相比之下，经SO₂处理的大鼠肝细胞中的酶泄漏情况不同，因为乳酸脱氢酶活性降低。肺细胞中的酶泄漏在各组之间没有差异，但低于肝细胞。在外源化合物代谢酶方面，主要是经NOₓ处理的动物中这些酶减少，即在肝脏中AHH、NDMA-D和GST减少，在肺中GST减少。对于经SO₂处理的动物，肝脏中的NDMA-D增加，肺中的GST减少。血清酶水平彼此之间差异不大，除了暴露于SO₂的动物中乳酸脱氢酶升高。
