Dashwood R H
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822.
Carcinogenesis. 1992 Jan;13(1):113-8. doi: 10.1093/carcin/13.1.113.
Chlorophyllin (CHL), a sodium/copper salt of chlorophyll used in the treatment of geriatric patients, exhibits potent antimutagenic 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 [2-14C]2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 50 mg/kg body wt) by single oral gavage. Covalent IQ-DNA binding in liver 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.
叶绿酸（CHL）是一种用于治疗老年患者的叶绿素钠/铜盐，在一系列体外和体内试验中均表现出强大的抗诱变活性。在Sprague-Dawley大鼠中，以抑制致癌物与DNA的结合为终点，研究了CHL的保护作用。通过单次口服灌胃给予动物CHL（150mg/kg体重）和[2-¹⁴C]2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ，50mg/kg体重）。给药后8、24和48小时测定肝脏中IQ与DNA的共价结合；与仅给予IQ的大鼠相比，CHL在这些时间点分别抑制结合58%、56%和46%。CHL处理的大鼠肝脏中IQ衍生放射性的总负荷降低，尿液和胆汁中消除的放射性标记总量也降低。然而，给予CHL的大鼠粪便中的消除量增加，无论是粪便二氯甲烷提取物中消除的总放射性标记还是未代谢IQ的量。最后，在饮用水中用CHL预处理，或在原位将CHL注射到离体肠段中，均可减少肠道对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相互作用并减少致癌物的摄取、分布和代谢，从而减弱大鼠肝脏中IQ与DNA的结合。结果表明，应进一步研究CHL的保护机制和可能的抗癌特性。
