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钒对7,12-二甲基苯并(a)蒽诱导的大鼠乳腺癌发生的化学预防作用:代表性肝相I和II异源物质代谢酶可能的参与情况

Vanadium chemoprevention of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis: probable involvement of representative hepatic phase I and II xenobiotic metabolizing enzymes.

作者信息

Bishayee A, Oinam S, Basu M, Chatterjee M

机构信息

Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.

出版信息

Breast Cancer Res Treat. 2000 Sep;63(2):133-45. doi: 10.1023/a:1006476003685.

Abstract

Vanadium, a non-platinum group metal and dietary micronutrient, is now proving to act as a promising antitumor agent. The present study was conducted to ascertain its antineoplastic potential against an experimental mammary carcinogenesis. Female Sprague-Dawley rats, at 50 days of age, were treated with 7,12-dimethylbenz(a)anthracene (DMBA) (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Vanadium (ammonium monovanadate) at the concentration of 0.5 ppm was supplemented in drinking water and given ad libitum to the experimental group immediately after the carcinogen treatment and it continued until the termination of the study (24 weeks for histological and biochemical observations and 35 weeks for morphological findings). It was found that vanadium treatment brought about a substantial protection against DMBA-induced mammary carcinogenesis. This was evident from histological findings that showed no sign of hyperplasia or abnormality after vanadium treatment. There was a significant reduction in incidence (P < 0.05), total number, multiplicity (P < 0.01) and size of palpable mammary tumors and delay in mean latency period of tumor appearance (P < 0.001) following vanadium supplementation compared to DMBA control. From the cumulative results of various hepatic biochemical indices namely, lipid peroxidation, reduced glutathione level, superoxide dismutase activity, cytochrome P450 content and glutathione S-transferase activity, the anticarcinogenic potential of vanadium was well reflected through stabilization of these parameters. Results of the study indicate that the anticarcinogenic activity of vanadium during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of phase I and II drug metabolizing enzymes. On the basis of the observed results, vanadium can be considered as a readily available, promising and novel cancer chemopreventive agent.

摘要

钒,一种非铂族金属和膳食中的微量营养素,目前正被证明是一种有前景的抗肿瘤剂。本研究旨在确定其对实验性乳腺癌发生的抗肿瘤潜力。50日龄的雌性斯普拉格-道利大鼠通过单尾静脉注射油乳剂接受7,12-二甲基苯并(a)蒽(DMBA)(0.5毫克/100克体重)处理。致癌物处理后,立即向实验组随意提供浓度为0.5 ppm的钒(偏钒酸铵)饮用水,并持续至研究结束(组织学和生化观察为24周,形态学观察为35周)。发现钒处理对DMBA诱导的乳腺癌发生有显著的保护作用。这从组织学结果中很明显,钒处理后没有增生或异常的迹象。与DMBA对照组相比,补充钒后可触及乳腺肿瘤的发生率(P < 0.05)、总数、多发性(P < 0.01)和大小显著降低,肿瘤出现平均潜伏期延迟(P < 0.001)。从各种肝脏生化指标的累积结果,即脂质过氧化、还原型谷胱甘肽水平、超氧化物歧化酶活性、细胞色素P450含量和谷胱甘肽S-转移酶活性来看,钒的抗癌潜力通过这些参数的稳定得到了很好的体现。研究结果表明,钒在DMBA引发的乳腺癌发生过程中的抗癌活性是通过改变肝脏抗氧化状态以及调节I相和II相药物代谢酶来介导的。基于观察到的结果,钒可被视为一种易于获得、有前景的新型癌症化学预防剂。

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