PROTECTION BY CHLOROPHYLLIN AGAINST THE COVALENT BINDING OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) TO RAT-LIVER DNA
PROTECTION BY CHLOROPHYLLIN AGAINST THE COVALENT BINDING OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) TO RAT-LIVER DNA
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DOI：
10.1093/carcin/13.1.113
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发表时间：
1992-01-01
期刊：
影响因子：
4.7
通讯作者：
DASHWOOD, RH
中科院分区：
文献类型：
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作者：
DASHWOOD, RH
叶绿素（CHL）是一种用于治疗老年患者的叶绿素钠/铜盐，在体内和体外的一系列试验中显示出强大的抗诱变活性。以抑制致癌物质- dna结合为终点，研究了CHL在Sprague-Dawley大鼠中的保护作用。动物单次灌胃给予CHL （150 mg/kg体wt）和[2-C-14]2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ， 50 mg/kg体wt）。分别在给药后8、24、48 h测定血清中IQ-DNA的共价结合；与单独给予智商的大鼠相比，CHL在这些时间分别抑制了58%、56%和46%的结合。在chl处理的大鼠中，iq来源的放射性总肝脏负荷减少，尿液和胆汁中消除的放射性标签总量也减少。然而，给予CHL的大鼠通过粪便消除的放射性标签总量和粪便中二氯甲烷提取物中未代谢的IQ量均有所增加。最后，在饮用水中预处理CHL，或将CHL原位注射到孤立的肠袢中，可减少肠道对IQ的吸收。总的来说，这些发现表明，当与致癌物同时给药时，CHL通过与肠道中的IQ相互作用，减少致癌物的摄取、分布和代谢，从而减弱大鼠肝脏中的IQ- dna结合。结果表明，CHL的保护机制和可能的抗癌特性有待进一步研究。
Chlorophyllin (CHL), a sodium/copper salt of chlorophyll used in the treatment of geriatric patients, exhibits potent anti-mutagenic activity in a range of assays in vitro and in vivo. The protective effects of CHL were studied in Sprague-Dawley rats using inhibition of carcinogen-DNA binding as an end-point. Animals were administered CHL (150 mg/kg body wt) and [2-C-14]2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 50 mg/kg body wt) by single oral gavage. Covalent IQ-DNA binding in fiver was determined 8, 24 and 48 h after dosing; CHL inhibited binding at these times by 58, 56 and 46% respectively, compared with rats given IQ alone. The total liver burden of IQ-derived radioactivity was reduced in CHL-treated rats, as was the total amount of radiolabel eliminated in the urine and bile. However, elimination via the feces was increased in rats given CHL, both in terms of total radiolabel eliminated and amount of unmetabolized IQ in dichloromethane extracts of feces. Finally, pretreatment with CHL in the drinking water, or injection of CHL into isolated loops of intestine in situ, reduced the absorption of IQ from the gut. Collectively, these findings indicate that, when administered simultaneously with the carcinogen, CHL attenuates IQ-DNA binding in rat liver by interacting with IQ in the gut and reducing carcinogen uptake, distribution and metabolism. The results suggest that further studies should be conducted with respect to the protective mechanisms and possible anti-carcinogenic properties of CHL.