Davis C D, Farb A, Thorgeirsson S S, Virmani R, Snyderwine E G
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland.
Toxicol Appl Pharmacol. 1994 Feb;124(2):201-11. doi: 10.1006/taap.1994.1024.
Cooked meat contains a number of mutagenic/carcinogenic heterocyclic amines, including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP). We recently observed that monkeys treated with IQ showed myocyte degeneration and mitochondrial changes. Thus, it was of interest to develop models to investigate heterocyclic amine cardiotoxicity. Primary cultures of fetal rat myocytes were exposed to the activated forms of the carcinogens (N-OH-IQ and N-OH-PhIP). LDH leakage increased in proportion to the carcinogen dose but was significantly greater in cells exposed to N-OH-IQ than that in cells exposed to N-OH-PhIP. Electron microscopy revealed that treated cells had swollen and irregular mitochondria and fewer organelles. However, DNA adducts, assessed using the 32P-postlabeling method, were significantly higher in myocytes exposed to N-OH-PhIP than in cells exposed to N-OH-IQ. The toxic effects of heterocyclic amines were also evaluated in rats given IQ or PhIP (100 mg/kg, po 10 doses over 2 weeks). Light microscopic 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.
熟肉含有多种诱变/致癌杂环胺，包括2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ）和2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）。我们最近观察到，用IQ处理的猴子出现了心肌细胞变性和线粒体变化。因此，开发模型来研究杂环胺的心脏毒性很有意义。将原代培养的胎鼠心肌细胞暴露于致癌物的活化形式（N-OH-IQ和N-OH-PhIP）。乳酸脱氢酶（LDH）泄漏量与致癌物剂量成比例增加，但暴露于N-OH-IQ的细胞中的LDH泄漏量明显高于暴露于N-OH-PhIP的细胞。电子显微镜显示，处理过的细胞线粒体肿胀且形态不规则，细胞器减少。然而，使用32P后标记法评估的DNA加合物在暴露于N-OH-PhIP的心肌细胞中明显高于暴露于N-OH-IQ的细胞。还对给予IQ或PhIP（100mg/kg，口服，2周内10剂）的大鼠进行了杂环胺毒性作用的评估。在暴露于IQ或PhIP的8只大鼠中，有7只出现了光镜和超微结构的心脏异常。对照动物的心脏形态正常，而经致癌物处理的动物有慢性炎症灶，伴有心肌细胞坏死、肌原纤维溶解和排列紊乱以及横管扩张。这些结果表明，食物诱变剂除了具有致癌性外，可能还在心脏变性中起作用。
