Altered Gene Expression in Rat Colonic Adenocarcinomas Induced in an Azoxymethane plus 2-Amino-1-Methyl-6-Phenylimidazo[4,5-<i>b</i>]- Pyridine Initiation-Promotion Model

Vol. 73, No. 3-4, 2007

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Laboratory Investigation

Altered Gene Expression in Rat Colonic Adenocarcinomas Induced in an Azoxymethane plus 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]- Pyridine Initiation-Promotion Model
Kenichiro Doi^a, Atsushi Hagihara^b, Min Wei^a, Takayuki Yunoki^a, Shoji Fukushima^c, Hideki Wanibuchi^a

^aDepartment of Pathology, Osaka City University Medical School, Osaka,
^bHepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, and
^cBioassay Research Center, Kanagawa, Japan

Address of Corresponding Author

Oncology 2007;73:252-260 (DOI: 10.1159/000127423)

Key Words

Azoxymethane
Microarray
PhIP
Rat colon carcinogenesis
RT-PCR

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant food-derived mutagenic/carcinogenic heterocyclic amine (HCA), has attracted particular attention as a probable human colon carcinogen. Some studies have shown that PhIP administered in the post-initiation phase is able to enhance rat colon carcinogenesis remarkably. To determine whether this genotoxicant leaves a DNA footprint in colon carcinogenesis, 6-week-old male F344 rats were first subcutaneously injected with azoxymethane (AOM) and then continuously treated with various doses (0-200 ppm) of PhIP added to their diet. Animals were killed at week 36 for histopathological examination, and colonic adenocarcinomas derived from animals receiving 0, 50 and 200 ppm PhIP were subjected to a novel three-dimensional (3D)-microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. A total of five candidate genes were identified in adenocarcinomas following 200 ppm of PhIP and AOM initiation, with a dose-dependent increment. Among them, Stat1 (signal transducer and activator of transcription 1) and VEGFc (vascular endothelial growth factor c) demonstrated statistically significant upregulation by real-time RT-PCR. In addition, HSP90 (heat shock protein 90) and VEGFa showed a non-significant tendency to increase. In summary, overexpression of Stat1, VEGF and other genes could be involved in PhIP-enhanced colon tumorigenesis in the post-initiation phase.

Author Contacts

Dr. Kenichiro Doi
Department of Pathology
Osaka City University Medical School
1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)
Tel. +81 6 6645 3737, Fax +81 6 6646 3093, E-Mail kenchan@med.osaka-cu.ac.jp

Article Information

Received: January 23, 2007
Accepted after revision: October 29, 2007
Published online: April 17, 2008
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 3, Number of References : 36

Medline Abstract (ID 18424890)

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