Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes
Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes
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DOI：
10.1207/s15327914nc4602_15
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Clifford, AJ
中科院分区：
文献类型：
--
作者：
Dingley, KH;Ubick, EA;Clifford, AJ
我们进行了一项研究，以评估饮食化学预防策略，以减少致癌物2-氨基-1-甲基-6-苯基-咪唑并[4，5-B]吡啶（PhIP）和2-氨基-3-甲基咪唑并[4，5-f]喹啉（IQ）的遗传毒性效应。PUP和IQ是在熟肉中发现的杂环胺（HCAs），可能是癌症的危险因素。典型的化学预防研究使用的致癌物剂量比人类日常摄入量高出数千倍。因此，我们给予低剂量的[C-14] PhIP和[H-3]IQ，并利用加速器质谱法以高灵敏度定量肝脏结肠、前列腺和血浆中的PhIP加合物以及肝脏和血浆中的IQ加合物。膳食补充苯乙基异硫氰酸酯（PEITC），染料木素，叶绿酸，番茄红素的能力，以减少加合物形成的[C-14]PhIP和[H-3]智商在大鼠进行了评估。我们还研究了治疗对第二阶段解毒酶谷胱甘肽S-转移酶（GST），UDP-葡萄糖醛酸转移酶（UGT），苯酚磺基转移酶（SULT）和醌还原酶（QR）的活性的影响。PEITC和叶绿酸显着降低PhIP-DNA加合物的水平在所有组织检查，这是反映了类似的变化PhIP结合到血液中的白蛋白。相反，染料木素和番茄红素往往增加PhIP加合物的水平。治疗没有显着改变IQ-DNA或蛋白质加合物在肝脏中的水平。除番茄红素外，治疗对一种或多种肝脏II期解毒酶的活性有一定影响。我们的结论是，PEITC和叶绿酸是保护PhIP诱导的遗传毒性后，低暴露剂量的致癌物，可能通过修改HCA代谢。
We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-l-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PUP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [C-14] PhIP and [H-3]IQ and utilized accelerator mass spectrometry to quantify PhIP adducts in the liver colon,prostate, and blood plasma and IQ adducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [C-14]PhIP and [H-3]IQ in rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism.