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Vol. 73, No. 3-4, 2007
Issue release date: April 2008
Section title: Laboratory Investigation
Oncology 2007;73:252–260
(DOI:10.1159/000127423)

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

Doi K. · Hagihara A. · Wei M. · Yunoki T. · Fukushima S. · Wanibuchi H.
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

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Article / Publication Details

First-Page Preview
Abstract of Laboratory Investigation

Received: 1/23/2007
Accepted: 10/29/2007
Published online: 4/17/2008

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL

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.


Article / Publication Details

First-Page Preview
Abstract of Laboratory Investigation

Received: 1/23/2007
Accepted: 10/29/2007
Published online: 4/17/2008

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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