Effects of Phenylethyl Isothiocyanate on Early Molecular Events in N-Nitrosomethylbenzylamine–Induced Cytotoxicity in Rat Esophagus

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. [Cancer Res 2007;67(13):6484-92]

Effects of a Black Raspberry Diet on Gene Expression in the Rat Esophagus

“…1. In agreement with our previous studies (5,6,11), statistical evaluation of the slides revealed no significant differences (Student's t-test > 0.01) in morphological appearance of esophagi between the 2 groups ( Table 1).…”

“…The data cutoff was set at a minimum 1.5-fold change to minimize false positives. In addition, the data were confirmed by comparison with mRNA levels obtained by quantitative reverse transcriptionpolymerase chain reaction using selected gene-specific primer pairs (see our previous report) (11). The probe accession tags were converted to Entrez GeneIDs (http://www.ncbi.nlm.nih.…”

“…The microarray analyses were carried-out using Agilent Rat Whole-Genome arrays (#G4131F, Agilent Technologies, Santa Clara, CA) with 60-mer oligonucleotide probes and over 41,000 transcripts as described before (11). Triplicate microarrays were completed for each group; each microarray was done using pooled RNA samples from 3 esophagi.…”

Trichloroethylene and Trichloroacetic Acid Regulate Calcium Signaling Pathways in Murine Embryonal Carcinoma Cells P19

“…While this was expected, due to Cyp2e1 interaction with signaling molecules involved in embryonic development (e.g., retinoic acid and ADH enzymes) [24], this set of data provided us with a tool to discriminate between effects of TCA and its parental compound. In addition, these results indicated how the effects of TCE on selected genes may be modulated and restored to a near to normal level by PEITC, as it has been shown in models of N-nitrosomethylbenzylamine-induced cytotoxicity in rat esophagus [25]. One limitation of this study is represented by the fact that we cannot establish the actual concentration of unmetabolized TCE in P19-exposed cells, due to the volatile nature of TCE.…”

Loss of ERα and FOXA1 expression in a progression model of luminal type breast cancer: Insights from PyMT transgenic mouse model

“…Phenethyl isothiocyanate (PEITC) is a compound that is derived from vegetables of the genus Brassica (7) and has demonstrable chemopreventive properties in rat esophagus, liver, and bladder cancers (8). It has several proposed mechanisms of action including induction of reactive oxygen species (ROS) secondary to disruption of the glutathione antioxidant system resulting in mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death (9).…”