Department of Medical Biochemistry, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Environ Toxicol Pharmacol. 2007 May;23(3):328-34. doi: 10.1016/j.etap.2006.12.004. Epub 2007 Jan 5.
Breast cancer is the major cause of cancer death in women worldwide. Environmental risk factors particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH) are likely to account for a much higher mortality. Xenobiotic metabolising enzymes in breast tissue are potentially important determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. The well known carcinogen 7,12-dimethylbenz(a)anthrazene of PAH family was given (25mg/ml) orally by gastric intubation to induce mammary carcinoma in Sprague-Dawley rats. Increased level of cytochromes (P(450), B(5)), EROD, PROD activities, Phase I biotransformation enzymes (NADPH-cytochrome (P(450)) reductase, NADPH-cytochrome (b(5)) reductase, epoxide hydrolase) and expression of CYP1A1, CYP1A2 and CYP1B1 in liver and breast tissue microsome were documented in DMBA treated group. Phase II enzyme activities (glutathione-S-transferase, gluthatione peroxidase, gluatathione reductase, UDP-glucuronyl transferease) were decreased markedly in cancerous rats. The nut extract of Semecarpus anacardium was administered orally (200mg/kg body wt/day) to the mammary carcinoma rats for 14 days. Drug treatment restored back the altered Phase I and II biotransformation enzymes thus achieving complete detoxification of the carcinogen. These findings suggest that S. anacardium can effectively modulate the catabolism of xenobiotics in rats.
乳腺癌是全球女性癌症死亡的主要原因。环境风险因素，特别是遗传毒性化学物质如多环芳烃（PAH），可能导致更高的死亡率。乳腺组织中的外来生物代谢酶可能是化学致癌物致突变作用易感性和乳腺癌对化疗反应的重要决定因素。众所周知的 PAH 家族致癌剂 7,12-二甲基苯并（a）蒽通过胃内插管以 25mg/ml 的剂量给予 Sprague-Dawley 大鼠，以诱导乳腺癌。DMBA 处理组记录到肝脏和乳腺组织微粒体中细胞色素（P450）、B5、EROD、PROD 活性、I 相生物转化酶（NADPH-细胞色素（P450）还原酶、NADPH-细胞色素（b5）还原酶、环氧化物水解酶）和 CYP1A1、CYP1A2 和 CYP1B1 的表达增加。癌症大鼠的 II 相酶活性（谷胱甘肽-S-转移酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、UDP-葡萄糖醛酸转移酶）显著降低。用 Semecarpus anacardium 的坚果提取物以 200mg/kg 体重/天的剂量经口给予乳腺癌大鼠 14 天。药物治疗使改变的 I 相和 II 相生物转化酶恢复正常，从而实现了致癌物的完全解毒。这些发现表明，S. anacardium 可以有效地调节大鼠中异生物的分解代谢。
