杂环胺：评估它们在与饮食相关的人类癌症中的作用。
Heterocyclic amines: evaluation of their role in diet associated human cancer.
作者信息
Gooderham N J, Murray S, Lynch A M, Edwards R J, Yadollahi-Farsani M, Bratt C, Rich K J, Zhao K, Murray B P, Bhadresa S, Crosbie S J, Boobis A R, Davies D S
机构信息
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
出版信息
Br J Clin Pharmacol. 1996 Jul;42(1):91-8. doi: 10.1046/j.1365-2125.1996.37513.x.
Abstract
- Heterocyclic amines are formed in parts per billion levels when meat is cooked. 2. The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food. 3. We have shown that MeIQx and PhIP, both in vitro and in vivo, are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines. 4. MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt, we have shown that PhIP induces a characteristic mutational 'fingerprint'. 5. MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.
摘要
- 肉类烹饪时会形成十亿分之几水平的杂环胺。2. 摄入熟食后，杂环胺MeIQx和PhIP能有效吸收进入体循环。3. 我们已表明，无论是在体外还是体内，MeIQx和PhIP都是人肝脏CYP1A2的底物，CYP1A2专门且有效地催化它们转化为具有基因毒性的羟胺。4. MeIQx和PhIP是前诱变剂。MeIQx是一种非常强大的细菌诱变剂，而PhIP是一种更有效的哺乳动物细胞诱变剂。使用哺乳动物细胞靶基因hprt，我们已表明PhIP会诱导出特征性的突变“指纹”。5. MeIQx和PhIP在生物测定中具有致癌性。在大鼠中由PhIP诱导的5/8结肠肿瘤的Apc基因中检测到了PhIP突变“指纹”。
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