STUDIES ON THE MYOCARDIAL EFFECTS OF HETEROCYCLIC ARYLAMINES

2-氨基-3-甲基咪唑对食蟹猴的长期治疗[4，5- 用于致癌测试的喹啉(IQ)揭示了心肌细胞的证据 伴或不伴炎症的坏死，心肌细胞肥大， 肌原纤维丢失和线粒体异常。这些发现提出了 熟肉中是否含有杂环芳胺的问题 可能与特发性心肌病有关。因此，它是 有兴趣开发研究杂环胺的模型 心脏毒性。将原代培养的胎儿心肌细胞暴露于 致癌物质N-羟基-IQ和N-羟基-PhIP的活化形式。乳酸脱氢酶 渗漏与致癌剂量成正比增加，但显著- 暴露于N-羟基IQ的细胞比暴露于N-羟基IQ的细胞 N-羟基苯丙氨酸。电子显微镜显示，处理过的细胞有 线粒体肿胀、不规则，细胞器减少。然而，DNA 加合物，用32-P-后标记方法评估，显著 N-羟基苯丙氨酸作用下的心肌细胞高于N-羟基-苯丙氨酸作用的细胞 羟基智商。杂环芳胺的毒性作用也是 对给予智商或PhIP(100 mg/kg，P.O.)的大鼠进行评估10倍)。轻微- 镜下和超微结构显示心脏异常的有7例 8只大鼠暴露于智商或PhIP。而对照组动物则有正常的 心脏形态，致癌物处理的动物有慢性 炎症伴心肌细胞坏死、肌原纤维溶解和紊乱， 和T小管扩张。这些结果表明，除了 作为致癌物质，食物诱变剂可能会在心脏退化中发挥作用。

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.