Research output: Contribution to journal › Article › peer-review
Infection with Opisthorchis felineus induces intraepithelial neoplasia of the biliary tract in a rodent model. / Gouveia, Maria João; Pakharukova, Maria Y.; Laha, Thewarach et al.
In: Carcinogenesis, Vol. 38, No. 9, 01.09.2017, p. 929-937.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Infection with Opisthorchis felineus induces intraepithelial neoplasia of the biliary tract in a rodent model
AU - Gouveia, Maria João
AU - Pakharukova, Maria Y.
AU - Laha, Thewarach
AU - Sripa, Banchob
AU - Maksimova, Galina A.
AU - Rinaldi, Gabriel
AU - Brindley, Paul J.
AU - Mordvinov, Viatcheslav A.
AU - Amaro, Teresina
AU - Santos, Lucio Lara
AU - da Costa, José Manuel Correia
AU - Vale, Nuno
N1 - © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically relevant species of the trematode family Opisthorchiidae, and the causative agent of opisthorchiasis felinea over an extensive range that spans regions of Eurasia. The International Agency for Research on Cancer classifies the infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis as group 1 agents and a major risk factor for cholangiocarcinoma. However, the carcinogenic potential of the infection with O. felineus is less clear. Here, we present findings that support the inclusion of O. felineus in the Group 1 list of biological carcinogens. Two discrete lines of evidence support the notion that infection with this liver fluke is carcinogenic. First, novel oxysterol-like metabolites detected by liquid chromatography-mass spectroscopy in the egg and adult developmental stages of O. felineus, and in bile, sera, and urine of liver fluke-infected hamsters exhibited marked similarity to oxysterol-like molecules known from O. viverrini. Numerous oxysterols and related DNA-adducts detected in the liver fluke eggs and in bile from infected hamsters suggested that infection-associated oxysterols induced chromosomal lesions in host cells. Second, histological analysis of liver sections from hamsters infected with O. felineus confirmed portal area enlargement, inflammation with severe periductal fibrosis and changes in the epithelium of the biliary tract characterized as biliary intraepithelial neoplasia, BilIN. The consonance of these biochemical and histopathological changes revealed that O. felineus infection in this rodent model induced precancerous lesions conducive to malignancy.
AB - The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically relevant species of the trematode family Opisthorchiidae, and the causative agent of opisthorchiasis felinea over an extensive range that spans regions of Eurasia. The International Agency for Research on Cancer classifies the infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis as group 1 agents and a major risk factor for cholangiocarcinoma. However, the carcinogenic potential of the infection with O. felineus is less clear. Here, we present findings that support the inclusion of O. felineus in the Group 1 list of biological carcinogens. Two discrete lines of evidence support the notion that infection with this liver fluke is carcinogenic. First, novel oxysterol-like metabolites detected by liquid chromatography-mass spectroscopy in the egg and adult developmental stages of O. felineus, and in bile, sera, and urine of liver fluke-infected hamsters exhibited marked similarity to oxysterol-like molecules known from O. viverrini. Numerous oxysterols and related DNA-adducts detected in the liver fluke eggs and in bile from infected hamsters suggested that infection-associated oxysterols induced chromosomal lesions in host cells. Second, histological analysis of liver sections from hamsters infected with O. felineus confirmed portal area enlargement, inflammation with severe periductal fibrosis and changes in the epithelium of the biliary tract characterized as biliary intraepithelial neoplasia, BilIN. The consonance of these biochemical and histopathological changes revealed that O. felineus infection in this rodent model induced precancerous lesions conducive to malignancy.
KW - Animals
KW - Bile Duct Neoplasms/blood
KW - Bile Ducts, Intrahepatic/parasitology
KW - Biomarkers, Tumor/blood
KW - Biopsy
KW - Carcinogenesis
KW - Cholangiocarcinoma/blood
KW - Chromatography, High Pressure Liquid
KW - Cricetinae
KW - DNA Adducts/blood
KW - Humans
KW - Male
KW - Neoplasms, Experimental/blood
KW - Opisthorchiasis/complications
KW - Opisthorchis/pathogenicity
KW - Oxysterols/blood
KW - CHOLANGIOCARCINOMA
KW - DNA-ADDUCTS
KW - LIVER FLUKE INFECTION
KW - CANCERS
KW - VIVERRINI
UR - http://www.scopus.com/inward/record.url?scp=85029744811&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgx042
DO - 10.1093/carcin/bgx042
M3 - Article
C2 - 28910999
AN - SCOPUS:85029744811
VL - 38
SP - 929
EP - 937
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 9
ER -
ID: 10068554