Iqbal M, Giri U, Athar M
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):557-63. doi: 10.1006/bbrc.1995.2006.
Fe-NTA is a known renal carcinogen. However, little is known about its carcinogenic potential in liver. In this study we for the first time show that Fe-NTA is a potent hepatic tumor promoter. Fe-NTA administration induced dose dependently the hepatic ornithine decarboxylase (ODC) activity several folds as compared to its activity in the saline-treated rats. Similarly, hepatic DNA synthesis which is measured as [3H]thymidine incorporation in DNA is also increased following Fe-NTA treatment. The effects of Fe-NTA were similar to other tumor promoters not only with respect to inducing ODC activity and [3H]thymidine incorporation in DNA but also in depleting antioxidant armory of the tissue. Fe-NTA depleted levels of glutathione to about 35% of the saline-treated control and activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase decreased significantly (45-55% of saline-treated control). Concomitant with the depletion in antioxidant armory, Fe-NTA augmented hepatic microsomal lipid peroxidation more than three folds. The pretreatment of rats with antioxidants BHA or BHT diminished the observed effects of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor promoter and acts through a mechanism involving oxidative stress.
三价铁-亚硝基三乙酸（Fe-NTA）是一种已知的肾致癌物。然而，关于其在肝脏中的致癌潜力却知之甚少。在本研究中，我们首次表明Fe-NTA是一种强效的肝脏肿瘤促进剂。与生理盐水处理的大鼠相比，给予Fe-NTA后，肝脏鸟氨酸脱羧酶（ODC）活性呈剂量依赖性增加数倍。同样，以DNA中[3H]胸腺嘧啶核苷掺入量衡量的肝脏DNA合成在Fe-NTA处理后也增加。Fe-NTA的作用不仅在诱导ODC活性和DNA中[3H]胸腺嘧啶核苷掺入方面与其他肿瘤促进剂相似，而且在耗尽组织的抗氧化防御方面也相似。Fe-NTA使谷胱甘肽水平降至生理盐水处理对照组的约35%，抗氧化酶过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和葡萄糖6-磷酸脱氢酶的活性显著降低（为生理盐水处理对照组的45-55%）。与抗氧化防御的耗竭同时发生的是，Fe-NTA使肝脏微粒体脂质过氧化增加了三倍多。用抗氧化剂丁基羟基茴香醚（BHA）或二丁基羟基甲苯（BHT）对大鼠进行预处理可减弱Fe-NTA的上述作用。我们的数据表明，Fe-NTA是一种强效的肝脏肿瘤促进剂，其作用机制涉及氧化应激。
