Faculty Collaboration Database

Effects of phenylethyl isothiocyanate on early molecular events in N-nitrosomethylbenzylamine-induced cytotoxicity in rat esophagus. Cancer Res 2007 Jul 01;67(13):6484-92

Date

07/10/2007

Pubmed ID

17616710

Pubmed Central ID

PMC3016711

DOI

10.1158/0008-5472.CAN-06-4531

Scopus ID

2-s2.0-34447131494 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During the 3rd week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h after the last treatment; esophagi were excised and processed for histologic grading, microarray and real-time PCR analysis. Histopathologic analysis showed that treatment of rats with PEITC had a protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2,261 genes that were differentially expressed in the NMBA-treated versus control esophagi and 1,936 genes in the PEITC + NMBA versus NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1,323 genes in NMBA-treated esophagus, the vast majority of which were modulated by PEITC to near-normal levels of expression. Measured changes in the expression levels of eight selected genes were validated using real-time PCR. Results from 12 microarrays indicated that PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone.

Author List

Reen RK, Dombkowski AA, Kresty LA, Cukovic D, Mele JM, Salagrama S, Nines R, Stoner GD

MESH terms used to index this publication - Major topics in bold

Animals
Anticarcinogenic Agents
Body Weight
Carcinogens
Dimethylnitrosamine
Esophageal Neoplasms
Esophagus
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome
Isothiocyanates
Oligonucleotide Array Sequence Analysis
Precancerous Conditions
Rats
Reverse Transcriptase Polymerase Chain Reaction