Effects of chlorophyllin on transport of dibenzo(a, l)pyrene, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and aflatoxin B1 across Caco-2 cell monolayers
Effects of chlorophyllin on transport of dibenzo(a, l)pyrene, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and aflatoxin B1 across Caco-2 cell monolayers
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DOI：
10.1016/j.tox.2003.11.008
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发表时间：
2004-03-01
期刊：
影响因子：
4.5
通讯作者：
Rodriguez-Proteau, R
中科院分区：
文献类型：
--
作者：
Mata, JE;Yu, Z;Rodriguez-Proteau, R
叶绿酸（CHL）是叶绿素的钠铜衍生物，能够与几种已知的致癌物形成强的非共价复合物。已证明CHL具有抗黄曲霉毒素B I（AF B（1））、二苯并（a，l）芘（DBP）和2-氨基-1-甲基-6-苯基咪唑- [4，5-B]吡啶（PhIP）的抗突变和抗癌作用，包括减少DNA加合物和肿瘤形成。已提出至少具有部分环结构的平面分子的摄取和/或代谢的改变作为CHL化学预防的作用机制。肠上皮转运的Caco-2细胞模型用于评价在0、1、10和100 μ M CHL存在下1 μ M DBP、AFB（1）和PhIP跨细胞单层的吸收。DBP和AFB（1）的渗透性（P1）从基底外侧到顶侧无显著差异（BL --> AP）与顶侧至基底侧相比（AP --> BL）隔室的DBP和AFB 1，然而，来自BL --> AP的PhIP的P1，1.26 x 10（5）+/- 2.10 x 10（6）cm/s，显著高于AP --> BL，5.83 x 10（6）+/- 7.56 x 10（7）cm/S，（p < 0.001），表明存在主动外排途径。在所有浓度下，DBP从AP -> BL室的转运均显著减少（P < 0.05）。加入100 μ M CHL可显著降低AFB（1）的AP -> BL转运（P < 0.05），而1 μ M或10 μ M CHL对AFB（1）无影响。络合研究表明，在转运缓冲液中，DBP与CHL的结合亲和力（K-b）高于AFB（1）与CHL的结合亲和力。PhIP 1与CHL的结合亲和力比AFB（1）或DBP低，加入CHL后，其AP -> BL转运没有显著改变。这些数据表明，黄曲霉毒素B（1）和DBP的转运可以被CHL抑制，这支持了CHL在肠道中与这些致癌物直接结合导致生物利用度降低的模型，作为癌症化学预防剂的一种作用机制。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Chlorophyllin (CHL) is a sodium copper derivative of chlorophyll that is capable of forming strong non-covalent complexes with several known carcinogens. Antimutagenic and anticarcinogenic effects, including reduced DNA adduct and tumor formation have been demonstrated for CHL against aflatoxin B I (AFB(1)), dibenzo(a,l)pyrene (DBP) and 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP). Alterations in uptake and/or metabolism of planar molecules with at least partial ring structure have been proposed as mechanisms of action for CHL chemoprevention. The Caco-2 cell model of intestinal epithelial transport was used to evaluate the absorption of 1 muM DBP, AFB(1) and PhIP across cell monolayers in the presence of 0, 1, 10, and 100 muM CHL. No significant differences were observed in the permeability (P,) of DBP and AFB(1) from the basolateral-to-apical (BL --> AP) compared to apical-to-basolateral (AP --> BL) compartments' for DBP and AFB1, however, the P, of PhIP from BL --> AP, 1.26 x 10(5) +/- 2.10 x 10(6)cm/s, was significantly higher than AP --> BL, 5.83 x 10(6) +/- 7.56 x 10(7) cm/S, (p < 0.001) suggesting an active efflux pathway. Transport of DBP from AP --> BL compartments was significantly reduced at all CHL concentrations (P < 0.05). AP --> BL transport of AFB(1) was significantly reduced by the addition of 100 muM CHL (P < 0.05) while 1 muM or 10 muM CHL had no effect. Complexation studies revealed a higher binding affinity (K-b) for DBP to CHL compared to AFB(1) to CHL in transport buffer. AP --> BL transport of PhIP,1 which has a lower binding affinity for CHL than AFB(1) or DBP, was not significantly altered by the addition of CHL. These data suggest that the transport of AFB(1) and DBP can be inhibited by CHL, which supports a model of direct binding in the intestinal tract of CHL to these carcinogens with resultant reduction of bioavailability as one mechanism of action as a cancer chemopreventive agent. (C) 2003 Elsevier Ireland Ltd. All rights reserved.