Potentiation by the human liver fluke, Opisthorchis viverrini, of the carcinogenic action of N-nitrosodimethylamine upon the biliary epithelium of the hamster

Flavell, David J.; Lucas, Sue

doi:10.1038/bjc.1982.313

Cited by 35 publications

(20 citation statements)

References 12 publications

(7 reference statements)

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“…In several of the hamster studies, although fluke infection per se did not induce liver cancer, the combination of liver fluke infection and exposure to various carcinogenic nitrosamines induced cholangiofibrosis, cholangiocarcinomas, and hepatocellular nodules (9,10,(46)(47)(48). The high prevalence of Helicobacter spp.…”

Section: Discussionmentioning

confidence: 99%

Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia in Hamsters Naturally Infected with a Novel Helicobacter Classified in the H. bilis Cluster

et al. 2009

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We recently described helicobacter-associated progressive, proliferative, and dysplastic typhlocolitis in aging (18-to 24-month-old) Syrian hamsters. Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of Helicobacter genusspecific DNA was noted by PCR in cecal and paraffin-embedded liver samples from aged hamsters by the use of Helicobacter-specific PCR primers. By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences form a genotypic cluster most closely related to Helicobacter sp. Flexispira taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged helicobacter-infected hamsters showed various stages of predominantly portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there was cellular atypia consistent with nodular dysplasia. The livers also exhibited a range of chronic active portal/interface and lobular inflammation, with significant portal hepatitis being present. The inflammation was composed of a mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic-active nature in these aged hamsters infected with Helicobacter spp. The isolation of novel Helicobacter spp., their identification by PCR from the diseased livers of aged hamsters, and their taxonomic classification as belonging to the Helicobacter bilis cluster strengthen the argument that H. bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans.We recently described progressive, proliferative, and dysplastic typhlocolitis in aging (18-to 24-month-old) Syrian hamsters (31). The lesions in these hamsters were more severe in the older animals aged 7 to 24 months than in the younger, 1-to 6-month-old hamsters. The presence of Helicobacter spp. in the large bowel of all 24 hamsters included in the study was confirmed by culture and Helicobacter-specific PCR (31). Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified in this study (31). Enterohepatic Helicobacter spp. are associated with the development of inflammatory bowel disease in mice and, as determined more recently, humans (2, 18, 27, 51). These helicobacters can also induce hepatitis and hepatocellular carcinoma in susceptible strains of mice (1,14,19). We undertook a study to examine in detail the histological profile of the livers of hamsters aged 18 to 24 months and to determine whether Helicobacter sp. DNA was present in their livers (31). In addition, we purchased a small number of 6-month-old hamsters from the same vendor which originally supplied the aged hamsters and examined them for the presence of Helicobacter spp. in their intestines and liver and whether inflammation was associated with the presence of Helicobacter spp. in these target tissues. We document t...

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Section: Discussionmentioning

confidence: 99%

Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia in Hamsters Naturally Infected with a Novel Helicobacter Classified in the H. bilis Cluster

et al. 2009

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“…Many other experimental studies have found that other animals infected with C. sinensis alone have never developed cholangiocarcinoma, although the livers of animals experimentally infected with C. sinensis developed adenomatous hyperplasia, periductal fibrosis, inflammatory infiltration, and mucin-secreting cell metaplasia (66,67). Therefore, it has been suggested that the induction of cholangiocarcinoma from Clonorchiasis may be species dependent (61) and that the liver fluke per se does not provide the sole carcinogenic stimulus leading to malignancy (28).…”

Section: Experimental Studiesmentioning

confidence: 99%

“…Some investigations (28,61,110,113) have reported synergism between liver fluke infection and exogenous chemical carcinogens with respect to cholangiocarcinoma development in hamsters. Lee et al (61) demonstrated a high incidence (75%) of cholangiocarcinoma in hamsters that were treated with N-nitrosodimethylamine and then infected with C. sinensis.…”

Section: Experimental Studiesmentioning

confidence: 99%

“…While these propositions seem plausible, it now appears that exogenous environmental carcinogens, which are ubiquitous in nature, are more important. The most extensively studied of these carcinogens in terms of the cholangiocarcinogenesis associated with liver fluke infection are N-nitroso compounds (28,61,62,112,113).…”

Section: Exogenous and Endogenous Chemical Carcinogensmentioning

confidence: 99%

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Clonorchiasis and Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis

et al. 2004

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Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis, which is promoting effect. In areas of endemic infection, more clonorchiasis cases are now diagnosed incidentally during radiological examinations such as cholangiography, ultrasonography, and computed tomography. Radiological findings are regarded as pathognomonic for clonorchiasis since they reflect the unique pathological changes of this disorder. These radiological examinations currently play important roles in the diagnosis, staging, and decision-making process involved in the treatment of cholangiocarcinoma. The morphological features and radiological findings of clonorchiasis-associated cholangiocarcinoma are essentially combinations of the findings for the two diseases. The morphological features of clonorchiasis- associated cholangiocarcinoma, observed in radiological examinations, do not differ from those of the usual cholangiocarcinoma. In patients diagnosed with or suspected to have clonorchiasis, radiological findings should be carefully scrutinized for occult cholangiocarcinoma

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“…Animal experiments showed that N-nitrosodimethylamine could induce CCA in the Syrian Golden hamster [23] . Although OV infection alone did not induce CCA, the OV infection enhanced CCA production by N-nitrosodimethylamine in the hamsters [24,25] . Actually, a small amount of nitrosamine was detected in the food [4] .…”

Section: Etiological and Enhancing Agents For Cholangiocarcinogenesismentioning

confidence: 99%

Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

Misawa

Honjo

You

et al. 2014

WJGP

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Cholangiocarcinoma (CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resection. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.

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Potentiation by the human liver fluke, Opisthorchis viverrini, of the carcinogenic action of N-nitrosodimethylamine upon the biliary epithelium of the hamster

Abstract: Images Fig. 2 Fig. 3

Cited by 35 publications

References 12 publications

Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia in Hamsters Naturally Infected with a Novel Helicobacter Classified in the H. bilis Cluster

Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia in Hamsters Naturally Infected with a Novel Helicobacter Classified in the H. bilis Cluster

Clonorchiasis and Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis

Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

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