title: DBT- and DBTO2-induced dysplasia and their associated proteomic alterations in the small intestines of Wistar rats.
abstract: Dibenzothiophene (DBT) and its oxidized derivative dibenzothiophene sulfone (DBTO2) are important representatives of polycyclic aromatic hydrocarbons (PAHs). Due to the importance of PAHs in oncogenesis and the lack of toxicological investigations related to DBT and DBTO2, this work proposes to assess their toxic and molecular effects caused by chronic treatment of Wistar rats. In parallel, their effects were compared to those caused by treatment with 1,2-dimethylhydrazine (DMH), a classic mutagenic agent. At the 14th day post-treatment, the animals were sacrificed and blood withdrawn for hematology and evaluation of liver and pancreatic functions. No significant alterations were observed. Nevertheless, histopathological analyses revealed dysplastic lesions in the intestines of animals treated with DBT and DBTO2. CD44 and carcinoembryonic antigen (CEA) staining demonstrated an approximately 3-fold increase in expression of both tissue markers for animals administered DBT, DBTO2, and DMH. A comparative two-dimensional gel analysis revealed additional 23 proteins exhibiting altered levels in the small intestines caused by exposure to DBT and DBTO2. At last, a protein-metabolite interaction map provided major insights into the metabolism of the dysplastic tissues. Our results provided strong evidence that DBT and its derivative could potentially act as cancer inducers, highlighting their toxicological and environmental relevance.
authors.affiliation: Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Campus Morro do Cruzeiro, Ouro Preto, Minas Gerais, Brasil.
authors.forename: Karina Taciana
authors.initials: KT
authors.lastname: Silva
authors.forename: Renata Alves
authors.initials: RA
authors.lastname: Oliveira-Castro
authors.forename: Vinícius Correa
authors.initials: VC
authors.lastname: Rodrigues
authors.forename: Wanderson Geraldo
authors.initials: WG
authors.lastname: de Lima
authors.forename: Cibele Velloso
authors.initials: CV
authors.lastname: Rodrigues
authors.forename: William
authors.initials: W
authors.lastname: Castro-Borges
authors.forename: Milton Hércules Guerra
authors.initials: MH
authors.lastname: Andrade
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D029681:Arabidopsis Proteins; D001219:Aspartate Aminotransferases / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D016213:Cyclins; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000633:toxicity*
chemical_list: D029681:Arabidopsis Proteins; D002272:Carcinoembryonic Antigen; D016213:Cyclins; D013876:Thiophenes; C582283:cyclin SDS protein, Arabidopsis; C058517:dibenzothiophene 5-oxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000681:Amylases; C016366:dibenzothiophene
keywords: CD44; Dibenzothiophene; cancer; carcinoembryonic antigen; dimethylhydrazine; polycyclic aromatic hydrocarbon