STUDIES ON THE MYOCARDIAL EFFECTS OF HETEROCYCLIC ARYLAMINES

用2-氨基-3-甲基咪唑[4，5-c] f]喹啉（IQ）致癌性试验显示肌细胞 坏死伴或不伴相关炎症，肌细胞肥大， 肌原纤维缺失和线粒体异常。 这些发现提出 熟肉中杂环芳香胺（哈斯） 可能与特发性心肌病有关 因此， 对开发研究杂环胺模型兴趣 心脏毒性 将胎儿心肌细胞的原代培养物暴露于 致癌物N-羟基-IQ和N-羟基-PhIP的活化形式。 LDH 泄漏量与致癌物剂量成比例增加，但显著增加， 暴露于N-羟基-IQ的细胞比暴露于 N-羟基-PhIP。 电子显微镜显示，处理过的细胞 线粒体肿胀、不规则，细胞器减少。 但dna 加合物，使用32-P-后标记方法评估，显著 暴露于N-羟基-PhIP的心肌细胞比暴露于N- 羟基智商 杂环芳胺的毒性作用也被 在给予IQ或PhIP（100 mg/kg，p.o. 10倍）。 轻微- 7例存在镜下和超微结构心脏异常， 八只老鼠暴露在IQ或PhIP中。 而对照组的动物有正常的 心脏形态学，致癌剂处理的动物有慢性 炎症伴肌细胞坏死、肌原纤维溶解和紊乱， 和T小管扩张。 这些结果表明，除了 食物中的突变物会致癌，可能会导致心脏退化。

Cynomolgus monkeys chronically treated with 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) for carcinogenicity testing revealed evidence of myocyte necrosis with and without associated inflammation, myocyte hypertrophy, myofibrillar loss and mitochondrial abnormalities. These findings raised the question of whether heterocyclic arylamines (HAAs) in cooked meats could be associated with idiopathic cardiomyopathies. Thus, it was of interest to develop models to investigate heterocyclic amine cardiotoxicity. Primary cultures of fetal myocytes were exposed to the activated forms of the carcinogens N-hydroxy-IQ and N-hydroxy-PhIP. LDH leakage increased in proportion to the carcinogen dose but was signifi- cantly greater in cells exposed to N-hydroxy-IQ than in cells exposed to N-hydroxy-PhIP. Electron microscopy revealed that treated cells had swollen and irregular mitochondria and fewer organelles. However, DNA adducts, assessed using the 32-P-postlabeling method, were significantly higher in myocytes exposed to N-hydroxy-PhIP than in cells exposed to N- hydroxy-IQ. The toxic effects of heterocyclic arylamines were also evaluated in rats given IQ or PhIP (100 mg/kg, p.o. 10x). Light micro- scopic and ultrastructural cardiac abnormalities were present in seven of eight rats exposed to IQ or PhIP. Whereas control animals had a normal cardiac morphology, carcinogen-treated animals had foci of chronic inflammation with myocyte necrosis, myofibrillar dissolution and disarray, and dilation of T-tubules. These results suggest that, in addition to being carcinogenic, food mutagens may play a role in cardiac degeneration.