Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens

Enzmann, H.; Brunnemann, Klaus D.; Iatropoulos, Michael J.; Shpyleva, Svitlana; Lukyanova, Natalia; Todor, I N; Moore, Malcolm A; Spicher, Karsten; Чехун, В Ф; Tsuda, Hiroyuki; Williams, Gary M.

doi:10.1016/j.etp.2012.09.007

Cited by 7 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kitaura et al (1999), analyzing Long-Evans rats, observed that the karyomegaly is a typical histological characteristic observed in (kidney) proximal tubular epithelium before tumor development. More recently, Enzmann et al (2013) showed that different carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK), evaluated in turkey eggs for in ovo carcinogenicity assay (IOCA), were responsible for the appearance of different hepatic alterations, including the hepatocellular karyomegaly. Therefore, these data signal the potential of tannery effluents to present carcinogenic characteristics (i.e., they are able to cause tumors in the liver) when animals are exposed to chronic and longer intake of such effluents.…”

Section: Resultsmentioning

confidence: 99%

Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

Souza¹,

Guimarães²,

Silva³

et al. 2016

Rev. ambiente água

View full text Add to dashboard Cite

The effluent produced in tanneries can cause environmental damage and public health problems when disposed of improperly. However, few toxicological studies have evaluated the effects of the intake of tannery wastewater by mammals. The objective of this study is the histological assessment of organs of C57Bl/J mice exposed to the intake of different concentrations of raw tannery effluents, beginning with the hypothesis that these effluents can cause damage to the histological structure of the organs. The animals were divided into the following groups: control (0% effluent) and exposed to 0.1%, 1%, and 5% raw tannery effluent diluted in water, for a period of 120 days. For the histopathological evaluations, samples of the liver, kidney, spleen, heart, and lung were collected, fixed, and stained by the hematoxylin and eosin staining techniques. No anomalies were observed in kidney, spleen, heart, and lung fragments. Alterations were observed only in liver fragments. Moderate hydropic degeneration was detected in animals exposed to tannery effluents, mainly in the periportal space. A large number of necrotic hepatocytes (p<0.05) were detected, especially in animals exposed to higher tannery effluent concentrations. Further, the largest number of hepatocytes with karyomegaly (p<0.05) was observed in animals exposed to the highest effluent concentrations. Our study suggests that the observed alterations are related to the intake of tannery effluents and that these effluents cause changes that lead to an increase of free radical production and direct aggressions to hepatocyte membranes as well as to the appearance of hepatocellular karyomegaly.

show abstract

Section: Resultsmentioning

confidence: 99%

Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

Souza¹,

Guimarães²,

Silva³

et al. 2016

Rev. ambiente água

View full text Add to dashboard Cite

show abstract

“…The results obtained revealed that chicken embryos show higher sensitivity to the toxic effects of NDEA, compared to those of the NDMA. A number of studies on the effects of NDEA on turkey and quail embryos have been carried out (Brunnemann et al, 2002;Enzmann et al, 1995;Enzmann et al, 1997;Enzmann et al, 2013;Williams et al, 2011). These in ovo experiments showed a significant increase of the absolute and relative liver weights of the carcinogen-treated avian embryos.…”

Section: Discussionmentioning

confidence: 99%

“…The in ovo experiments are more rapid, less expensive and safer for the personnel than the in vivo experiments in rodents. In the in ovo carcinogenicity studies, turkey and quail embryos were most frequently used as experimental models (Enzmann et al, 1998;Enzmann et al, 1997;Enzmann et al, 1996, Enzmann et al, 1992, Enzmann et al, 2013. The development of preneoplastic FAH was also found in the liver of chicken embryos after treatment with organic (Georgieva et al, 2012) and inorganic carcinogenic chemicals (Kril et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

In ovo hepatocarcinogenicity of N-nitrosodimethylamine and N-nitrosodimethylamine in White Leghorn chickens

Kril

Georgieva

Nikolov

et al. 2018

J Hellenic Vet Med Soc

View full text Add to dashboard Cite

Avian embryos have been gaining an increasing scientific interest as a valuable model system for the experimental cancer research that could contribute to a significant reduction of the number of laboratory animals. In the present study, the liver lesions induced by N-nitrosodimethylamine and N-nitrosodiethylamine in 15I line, White Leghorn embryos were identified and studied by routine histopathological method s. Foci of altered hepatocytes with basophilic and eosinophilic phenotype, well known as preneoplastic alterations were identified in the avian embryonal livers after in ovo exposure to both N-nitroso compounds. These studies were further extended by histopathological, haematological and biochemical examinations on the effects of N-nitrosodimethylamine in chickens hatched from carcinogen-inoculated eggs. In addition to the preneoplastic lesions observed in the avian livers, proliferations of oval and hepatocellular carcinoma cells, with clearly expressed signs of malignancy were found. The in ovo application of the chemical carcinogen was found to affect both hematological and blood biochemistry parameters measured in experimental birds. The established conditions such as thrombocytopenia and increased levels of liver enzymes, as an essential part of the paraneoplastic syndrome, were associated with the process of hepatocarcinogenesis. The results of this study confirm the preneoplastic nature of the focal lesions in embryonal avian liver and their progression to liver neoplastic alterations after a single in ovo application of known hepatocarcinogens. Moreover, the results indicate that 15I line, White Leghorn embryos are anew, valuable in ovo model for studies on hepatocarcinogenicity of chemical compounds and underline the importance of research on the development of different avian models of carcinogenicity.

show abstract

“…The IOCA provides an aseptic intact developing organism, which is independent of maternal influences. In its current validated protocol, the assay involves a single dose followed by 24 days of incubation (Enzmann et al, 2013). The results obtained with several chemicals are supported by the demonstration that the turkey fetal liver expresses xenobiotic biotransformation enzymes that mediate DNA adduct formation (Perrone et al, 2004).…”

mentioning

confidence: 99%

“…Several testing approaches have been reported. The In Ovo Carcinogenicity Assessing (IOCA) assay, which has a turkey egg fetal liver as the target tissue, has shown responsiveness to carcinogenic chemicals (Enzmann et al, 1992(Enzmann et al, , 2013Williams et al, 2011a). The IOCA provides an aseptic intact developing organism, which is independent of maternal influences.…”

mentioning

confidence: 99%

Chicken Fetal Liver DNA Damage and Adduct Formation by Activation-Dependent DNA-Reactive Carcinogens and Related Compounds of Several Structural Classes

Williams

Duan

Brunnemann

et al. 2014

Toxicological Sciences

View full text Add to dashboard Cite

The chicken egg genotoxicity assay (CEGA), which utilizes the liver of an intact and aseptic embryo-fetal test organism, was evaluated using four activation-dependent DNA-reactive carcinogens and four structurally related less potent carcinogens or non-carcinogens. In the assay, three daily doses of test substances were administered to eggs containing 9-11-day-old fetuses and the fetal livers were assessed for two endpoints, DNA breaks using the alkaline single cell gel electrophoresis (comet) assay and DNA adducts using the (32)P-nucleotide postlabeling (NPL) assay. The effects of four carcinogens of different structures requiring distinct pathways of bioactivation, i.e., 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (B[a]P), and diethylnitrosamine (DEN), were compared with structurally related non-carcinogens fluorene (FLU) and benzo[e]pyrene (B[e]P) or weak carcinogens, aflatoxin B2 (AFB2) and N-nitrosodiethanolamine (NDELA). The four carcinogens all produced DNA breaks at microgram or low milligram total doses, whereas less potent carcinogens and non-carcinogens yielded borderline or negative results, respectively, at higher doses. AAF and B[a]P produced DNA adducts, whereas none was found with the related comparators FLU or B[e]P, consistent with comet results. DEN and NDELA were also negative for adducts, as expected in the case of DEN for an alkylating agent in the standard NPL assay. Also, AFB1 and AFB2 were negative in NPL, as expected, due to the nature of ring opened aflatoxin adducts, which are resistant to enzymatic digestion. Thus, the CEGA, using comet and NPL, is capable of detection of the genotoxicity of diverse DNA-reactive carcinogens, while not yielding false positives for non-carcinogens.

show abstract

Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens

Cited by 7 publications

References 38 publications

Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

Histopathological assessment of C57Bl/J mice organs exposed to tannery effluents

In ovo hepatocarcinogenicity of N-nitrosodimethylamine and N-nitrosodimethylamine in White Leghorn chickens

Chicken Fetal Liver DNA Damage and Adduct Formation by Activation-Dependent DNA-Reactive Carcinogens and Related Compounds of Several Structural Classes

Contact Info

Product

Resources

About