Heterocyclic amines: Evaluation of their role in diet associated human cancer

被引:38
作者
Gooderham, NJ
Murray, S
Lynch, AM
Edwards, RJ
YadollahiFarsani, M
Bratt, C
Rich, KJ
Zhao, K
Murray, BP
Bhadresa, S
Crosbie, SJ
Boobis, AR
Davies, DS
机构
关键词
heterocyclic amines; MeIQx; DiMeIQx; PhIP; CYYP1A2; bioavailability; metabolism; mutagenicity; carcinogenicity;
D O I
10.1046/j.1365-2125.1996.37513.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 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 Ape gene of 5/8 colonic rumours induced by PhIP in rats.
引用
收藏
页码:91 / 98
页数:8
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