Carcinogenic risk of heterocyclic amines in combination - Assessment with a liver initiation model

Akihiro Hirata, Tetsuya Tsukamoto, Hiroki Sakai, Shinji Takasu, Hisayo Ban, Toshio Imai, Yukari Totsuka, Rena Nishigaki, Keiji Wakabayashi, Tokuma Yanai, Toshiaki Masegi, Masae Tatematsu

研究成果: Article査読

10 被引用数 (Scopus)


Carcinogenic potential of heterocyclic amines (HCAs) was investigated using an in vivo 5-week initiation assay with quantitative evaluation of glutathione S-transferase placental form (GST-P) positive foci in rat liver. Numbers of GST-P positive foci were significantly increased with individual administration of six different HCAs, indicating utility of the assay. It was therefore applied to investigate risk with multiple HCAs in combination. Unexpectedly, concomitant treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) did not result in any additive carcinogenicity. In the rats taking MeIQx prior to PhIP the value was almost equal to the sum total of individual data, indicating additive initiation activities. In contrast, simultaneous or prior administration of PhIP rather exerted inhibitory effects on the carcinogenic potential of MeIQx. Moreover, microarray and quantitative RT-PCR assessment revealed that PhIP induced cytochrome P450 1A1, responsible for both activation and detoxification of HCAs, more strongly than MeIQx. It is noteworthy that complex exposure to multiple HCAs is not necessarily associated with increased risk of carcinogenesis because they are simultaneously and continuously ingested under normal circumstances.

ジャーナルFood and Chemical Toxicology
出版ステータスPublished - 06-2008

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

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