Singla A K, Kaur I P
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
Indian J Exp Biol. 2002 Dec;40(12):1365-72.
Curcumin (C) and its natural analogues demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC), known for their potent anti-inflammatory, antioxidant, antimutagenic and anticarcinogenic effects, were tested for their possible inhibitory effects against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor induced rat liver S9 homogenate. In the present investigations, curcumin as well as its two natural analogues i.e., dmC and bdmC were found to be highly effective in suppressing genotoxicity of all the tested cooked food mutagens in a dose-dependent manner, in both the frame shift (TA98) as well as base pair mutation sensitive (TA100) strains of S. typhimurium. However, bdmC appeared to be a relatively less active antimutagen compared to C and dmC. More than 80% inhibition of mutagenicity was observed at 200 microg/plate in case of C and dmC in both TA98 and TA100 against all tested cooked food mutagens. Where as, bdmC showed 39-79% inhibition in TA100 and 60-80% inhibition in TA98, at a dose of 200 microg/plate. These findings warrant further biochemical, enzymatic and in vivo investigations in animal models as well as in humans to establish the chemoprotective effect of these agents against mutagenic heterocyclic amines found in cooked food.
姜黄素（C）及其天然类似物去甲氧基姜黄素（dmC）和双去甲氧基姜黄素（bdmC），因其具有强大的抗炎、抗氧化、抗诱变和抗癌作用而闻名。在存在艾氏剂诱导的大鼠肝脏S9匀浆的情况下，利用鼠伤寒沙门氏菌/回复突变试验，在鼠伤寒沙门氏菌的TA98和TA100菌株中，测试了它们对七种烹饪食物诱变剂（杂环胺）的可能抑制作用，这七种诱变剂分别是：2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ）、2-氨基-3,4-二甲基咪唑[4,5-f]喹啉（MeIQ）、2-氨基-3,8-二甲基咪唑[4,5-f]喹喔啉（MeIQx）、3-氨基-1,4-二甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-1）、3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-2）、2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）和2-氨基-6-甲基二吡啶并[1,2-a:3',2'-d]咪唑（Glu-P-1）。在本研究中，发现姜黄素及其两种天然类似物，即dmC和bdmC，在鼠伤寒沙门氏菌的移码突变（TA98）以及碱基对突变敏感（TA100）菌株中，均能以剂量依赖的方式高效抑制所有测试烹饪食物诱变剂的遗传毒性。然而，与C和dmC相比，bdmC似乎是一种活性相对较低的抗诱变剂。在TA98和TA100中，对于所有测试的烹饪食物诱变剂，在200微克/平板的剂量下，C和dmC均观察到超过80%的诱变活性抑制。而在200微克/平板的剂量下，bdmC在TA100中表现出39 - 79%的抑制，在TA98中表现出60 - 80%的抑制。这些发现需要在动物模型以及人类中进行进一步的生化、酶学和体内研究，以确定这些试剂对烹饪食物中发现的诱变杂环胺的化学保护作用。
