3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a group 2B carcinogen characterized by the International Agency for Research on Cancer (IARC) and great efforts have been taken to reduce Trp-P-1 mutagenicity to humans. In this study, the effect of a reduction of Trp-P-1 on intestinal absorption as a promising strategy was investigated. The data showed that when 20 mM Trp-P-1 cotransported with 10 mM of sodium carboxymethyl cellulose (CMC), xanthan gum, or carrageenan, the absorption rate of Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1 cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal tissues, correspondingly. These 3 polysaccharides also reduced pharmacokinetic parameters, that is, Cmax , AUC0-t , and AUC0-∞ , after Trp-P-1 was given to rats intragastrically. However, gum arabic did not exhibit similar effects on Trp-P-1 absorption in vitro or in vivo. The Ames test showed that these 3 polysaccharides reduced Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but gum arabic did not. Isothermal titration calorimetry assay indicated that Trp-P-1 interacted with these 3 polysaccharides. Thermodynamic study showed that the actual value of △H <0, but its absolute value greater than the corresponding value of T∆S, suggest a specific interaction between Trp-P-1 and these 3 polysaccharides, probably through the hydrogen bond and/or ion interaction. Reduction of Trp-P-1 intestinal absorption using food additives could be one of the strategies to suppress Trp-P-1-induced carcinogenesis in human. PRACTICAL APPLICATION 1.This study provides insightful information for the food industry how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl cellulose affect the absorption of Trp-P-1. 2.This study also provides novel information regarding a better formulation for meat products to reduce Trp-P-1 absorption.

中文翻译：

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多糖在体外和体内降低 3-Amino-1,4-Dimethyl-5H-Pyrido[4,3-b]Indole 的吸收和致突变性

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) 是国际癌症研究机构 (IARC) 鉴定的 2B 组致癌物用于降低 Trp-P-1 对人类的致突变性。在这项研究中，研究了减少 Trp-P-1 对肠道吸收的影响作为一种有前途的策略。数据显示，当 20 mM Trp-P-1 与 10 mM 羧甲基纤维素钠 (CMC)、黄原胶或角叉菜胶共转运时，Trp-P-1 的吸收率降低了 31.5%、49.5% 或 72.9分别在 MDCK-MDR1 细胞单层中的百分比；大鼠肠组织中分别为 64.6%、83.4% 或 64.1%。在大鼠灌胃 Trp-P-1 后，这 3 种多糖还降低了药代动力学参数，即 Cmax 、AUC0-t 和 AUC0-∞ 。然而，阿拉伯树胶在体外或体内对 Trp-P-1 吸收没有表现出类似的影响。Ames 试验表明，这 3 种多糖降低了 Trp-P-1 对鼠伤寒沙门氏菌 TA98 的致突变性，而阿拉伯树胶则没有。等温滴定量热分析表明Trp-P-1与这3种多糖相互作用。热力学研究表明△H的实际值<0，但其绝对值大于T△S的对应值，表明Trp-P-1与这3种多糖之间存在特定的相互作用，可能通过氢键和/或离子相互作用。使用食品添加剂减少 Trp-P-1 肠道吸收可能是抑制 Trp-P-1 诱导的人类致癌作用的策略之一。实际应用 1.这项研究为食品工业提供了深刻的信息，阿拉伯树胶、黄原胶、kappa 角叉菜胶和羧甲基纤维素钠会影响 Trp-P-1 的吸收。2.本研究还提供了有关更好的肉制品配方以减少 Trp-P-1 吸收的新信息。