Neonatal exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine via breast milk or directly induces intestinal tumors in multiple intestinal neoplasia mice
Neonatal exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine via breast milk or directly induces intestinal tumors in multiple intestinal neoplasia mice
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DOI：
10.1093/carcin/20.7.1277
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发表时间：
1999-07-01
期刊：
影响因子：
4.7
通讯作者：
Alexander, J
中科院分区：
文献类型：
--
作者：
Paulsen, JE;Steffensen, IL;Alexander, J
我们研究了食物诱变剂2-氨基-1-甲基-6-苯基咪唑[3，5-B]吡啶（PhIP）是否会增加新生C57 BL/6 J-Min/+小鼠（家族性腺瘤性息肉病的小鼠模型）的肠道肿瘤发生。Min /+小鼠是腺瘤性息肉病大肠杆菌基因中无义突变的杂合子，并自发发生多发性肠道腺瘤，主要发生在小肠。新生Min/ +小鼠（3-6日龄）通过哺乳母鼠的母乳暴露于PhIP，每周注射3次50 mg/kg PhIP，每次8 s，或直接注射25或50 mg/kg PhIP，在同一时期，在11周龄时，对肠道肿瘤的数量、直径和位置进行评分，值得注意的是，通过母乳接触PhIP的Min/ +小鼠中小肠肿瘤数量增加2- 4倍（P < 0.001）。据我们所知，这是首次报道PhIP通过母乳接触PhIP暴露的大鼠诱发肿瘤。50 mg/kg的PhIP可使小鼠小肠肿瘤数增加6 ~ 9倍（P < 0.001），肿瘤直径略有增大（P <0.001）。在结肠中，在通过母乳暴露于PhIP的Min/ +小鼠中观察到肿瘤数量增加3至4倍（P = 0.004），直接暴露于50 mg/kg PhIP导致结肠肿瘤数量增加2- 6倍与对照组相比，PhIP诱导的结肠肿瘤位于远端，直径较小（P = 0.014）（P < 0.05），与先前的研究相反，其中PhIP在成年Min/ +小鼠中仅显示出中度致瘤作用，本研究证明了PhIP在经母体暴露的Min/ +小鼠中的强烈致瘤作用，甚至在通过来自PhIP暴露的母鼠的母乳暴露之后。
We examined whether the food mutagen 2-amino-1-methyl-6-phenylimidazo [3,5-b]pyridine (PhIP) could increase intestinal tumorigenesis in neonatal C57BL/6J-Min/+ mice, a murine model for familial adenomatous polyposis, Min /+ mice are heterozygous for a nonsense mutation in the adenomatous polyposis coli gene and spontaneously develop multiple intestinal adenomas, primarily in the small intestine. Neonatal Min/ + mice (3-6 days old) were exposed to PhIP via breast milk from lactating dams given 8 s,c, injections of 50 mg/kg PhIP three times a week or to 8 s,c, injections of 25 or 50 mg/kg PhIP directly, over the same period, At the age of 11 weeks, the number, diameter and location of the intestinal tumors were scored, Remarkably, a 2- to 4-fold increase in the number of small intestinal tumors was seen in Min/ + mice exposed to PhIP via breast milk (P < 0.001), To our knowledge, this is the first time PhIP has been reported to induce tumors following exposure via breast milk from PhIP-exposed darns. Upon direct exposure to 50 mg/kg PhIP, a 6- tb 9-fold increase in the number of small intestinal tumors was observed (P < 0.001), The diameter of the PhIP-induced small intestinal tumors was slightly increased (P < 0.001). In the colon, a 3- to 4-fold increase in the number of tumors was seen in Min/ + mice exposed to PhIP via breast milk (P = 0.004), Direct exposure to 50 mg/kg PhIP caused a 2- to 6-fold increase in the number of colonic tumors (P = 0.014), The PhIP-induced colonic tumors were located more distally and displayed a smaller diameter than the tumors from the controls (P < 0.05), In contrast to a previous study, where PhIP showed only a moderate tumorigenic effect in adult Min/ + mice, the present study demonstrates a strong tumorigenic effect of PhIP in neonatally exposed Min/ + mice, even after exposure via breast milk from PhIP-exposed dams.