Regional mutagenicity of heterocyclic amines in the intestine:: mutation analysis of the cII gene in lambda/lacZ transgenic mice
Regional mutagenicity of heterocyclic amines in the intestine:: mutation analysis of the cII gene in lambda/lacZ transgenic mice
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DOI：
10.1016/s1383-5718(03)00134-7
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发表时间：
2003-08-05
影响因子：
1.9
通讯作者：
Ohnishi, Y
中科院分区：
文献类型：
--
作者：
Itoh, T;Kuwahara, T;Ohnishi, Y
转基因小鼠的测试表明，尽管小鼠的肠道对致癌具有抵抗力，但它对一些杂环胺(HCAs)的诱变性很敏感。然而，人们对这种敏感性的水平和局限性知之甚少。本文研究了HCAs-2-amino-1-methyl-6-phenylimidazo[4，5-b]pyridine(PhIP)盐酸盐、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)和3-氨基-1-甲基-5H-吡啶并[4，3-b]吲哚(Trp-P-2)醋酸酯(Trp-P-2)对雄性MUTA(TM)小鼠肠道的致突变性。最后一次给药两周后，我们从小肠、盲肠和结肠分离上皮细胞，并分析LacZ和CII转基因突变。PhIP增加了所有样品的LacZ突变频率(Mf)，在小肠中，CII和LacZ MFS具有可比性。在CII基因中，G：C到T：A和G：C到C：G的转换是PhIP诱导的典型突变(在PhIP致癌的大鼠结肠中也有报道)。在小肠中，PhIP使CII Mf增加到对照组的4倍，但IQ、MelQ和Trp-P-2没有明显的致突变作用。在盲肠，智商和MeIQ诱导的CII MFS分别是对照组的1.9倍和2.7倍。MeIQ诱导的大鼠结肠微渗漏是对照组的3.1倍。致突变性顺序为PhIP>；MeIQ>；IQ；Trp-P-2不显著增加任何组织中的Mf。盲肠是HCA致突变最敏感的器官。(C)2003爱思唯尔B.V.保留所有权利。
Transgenic mouse assays have revealed that the mouse intestine, despite its resistance to carcinogenesis, is sensitive to the mutagenicity of some heterocyclic amines (HCAs). Little is known, however, about the level and localization of that sensitivity. We assessed the mutagenicity of four orally administered (20 mg/kg per day for 5 days) HCAs-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) hydrochloride, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4dimethylimidazo[4,5-f]quinoline (MeIQ), and 3-amino-1-methyl-5H-pyrido [4,3-b] indole (Trp-P-2) acetate-in the intestine of male Muta(TM)Mice. Two weeks after the last administration, we isolated epithelium from the small intestine, cecum, and colon and analyzed lacZ and cII transgene mutations. PhIP increased the lacZ mutant frequency (MF) in all the samples, and in the small intestine, cII and lacZ MFs were comparable. In the cII gene, G:C to T:A and G:C to C:G transversions were characteristic PhIP-induced mutations (which has also been reported for the rat colon, where PhIP is carcinogenic). In the small intestine, PhIP increased the cII MF to four-fold that of the control, but IQ, MelQ, and Trp-P-2 did not have a significant mutagenic effect. In the cecum, cII MFs induced by IQ and MeIQ were 1.9 and 2.7 times those in the control, respectively. The MF induced by MeIQ in the colon was 3.1 times the control value. Mutagenic potency was in the order PhIP > MeIQ > IQ; Trp-P-2 did not significantly increase the MF in any tissue. The cecum was the most susceptible organ to HCA mutagenicity. (C) 2003 Elsevier B.V. All rights reserved.