title: Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt andApc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis.
abstract: Apc-mutated Pirc rats, spontaneously developing intestinal tumours, are resistant to 1,2-dimethylhydrazine- (DMH-) induced colon apoptosis. To understand this phenomenon, we analyzed the expression of genotoxic stress-related genesMgmt,Gsta1, andGstp1in the colon of wt and Pirc rats in basal conditions and 24 h after DMH; plasmatic oxidant/antioxidant status was also evaluated. After DMH,Mgmtexpression was increased in both genotypes but significantly only in wt rats;Gsta1expression was significantly increased in both genotypes.Gstp1expression did not vary after DMH but was lower in Pirc rats. Moreover, for each genotype, we studied by microarray technique whole gene expression profile after DMH. By unsupervised cluster analysis, 28 genes were differentially modulated between the two genotypes. Among them were interferon-induced genesIrf7,Oas1a,Oasl2, andIsg15and the transcription factorTaf6l, overexpressed in DMH-treated wt rats and unchanged in Pirc rats. RT-PCR confirmed their overexpression in DMH-treated wt rats and showed a slighter variation in DMH-treated Pirc rats. Taken together, despite a blunted induction ofIrf7,Oas1a, andMgmt, defective apoptosis in Pirc rats 24 h after DMH is not mirrored by major differences in gene expression compared with wt rats.
authors.affiliation: NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
authors.forename: Angelo Pietro
authors.identifier: 0000-0002-1503-4372
authors.initials: AP
authors.lastname: Femia
authors.affiliation: NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Luceri
authors.affiliation: NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Lodovici
authors.affiliation: NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Crucitta
authors.affiliation: NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Caderni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D003106:Colon / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000235:genetics; D017491:Genes, APC / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D059467:Transcriptome / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D015254:DNA Modification Methylases; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha