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ToxSci Advance Access published online on January 5, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi079
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Toxicological Sciences © Society of Toxicology 2005; all rights reserved.
Received November 19, 2004
Accepted January 2, 2005

Carcinogenicity

Induction of colon tumors in C57BL/6Jmice fed MeIQx, IQ or PhIP followed by dextran sulfate sodium treatment

Akiyoshi Nishikawa 1*, Takayoshi Imazawa 1, Yuichi Kuroiwa 1, Yasuki Kitamura 1, Keita Kanki 1, Yuji Ishii 1, Takashi Umemura 1, and Masao Hirose 1

1 Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan

* To whom correspondence should be addressed.
Akiyoshi Nishikawa, E-mail: nishikaw{at}nihs.go.jp


  Abstract

Heterocyclic amines (HCAs) have been shown to induce tumors in several organs of rodents, but except for MeIQ and PHIP, other HCAs such as MeIQx and IQ consistently failed to induce colon tumors in mice whereas MeIQ, IQ and PhIP exerted colon tumorigenicity in rats. Recently, we found that dietary MeIQx induces genotoxicity in the colon as well as the liver of 2 different types of reporter gene transgenic mice at subcarcinogenic doses such as 300 ppm. However, in the present study, dietary MeIQx did not significantly induce any tumors in C57BL/6J mice or gpt delta mice even when fed at 300 ppm for 78 weeks, suggesting that the treatment of MeIQx alone was not sufficient to promote colon tumors. In order to clarify a possibility whether such HCAs can induce colon tumors, C57BL/6J mice were fed MeIQx, IQ or PhIP at a dose of 300 ppm for 12 weeks, and thereafter twice received 1-week treatment with dextran sulfate sodium (DSS) apart 2 weeks. After twenty weeks, colon tumors including adenocarcinomas were found at incidences of 22%, 24% and 45% in the groups receiving MeIQx, IQ and PhIP, respectively, which were significantly (P<0.05 or 0.01) different from the DSS alone value (0%). Thus our results clearly indicate that in addition to PhIP, MeIQx and IQ can induce colon tumors in mice under an experimental condition promoting colon tumors.

Keywords: MeIQx; heterocyclic amime; colon tumor; dextran sulfate sodium; mouse.
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