In ovo carcinogenicity assay (IOCA): evaluation of mannitol, caprolactam and nitrosoproline

Brunnemann, Klaus D.; Enzmann, Harald; Perrone, Carmen E.; Iatropoulos, Michael J.; Williams, Gary M.

doi:10.1007/s00204-002-0380-4

Cited by 13 publications

(6 citation statements)

References 16 publications

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“…In addition, clearly expressed hyperplasia of cholangiocytes was regularly observed in the liver of experimental birds. Similar histopathological alterations were found previously in quail embryos, in ovo treated with hepatocarcinogens (Brunnemann et al, 2002;Enzmann et al, 1996). In addition to the preneoplastic and hyperplasic alterations affecting hepatocytes and cholangiocytes, respectively, the development of neoplastic processes evidenced by the appearance of proliferations composed of oval and hepatocyte-like carcinoma cells were identified in the experimental birds.…”

Section: Resultssupporting

confidence: 89%

“…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%

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

Kril

Georgieva

Nikolov

et al. 2018

J Hellenic Vet Med Soc

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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.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

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

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“…A possible short-term bioassay to examine toxic and carcinogenic effects of chemicals in liver involves turkey or quail embryos, also known as the in ovo carcinogenicity assay (IOCA) (Enzmann and Brunnemann 1997;Enzmann et al 1998a, b;Brunnemann et al 2002). IOCA has the advantage that it is rapid and inexpensive since experiments can be conducted within 24 days and with single doses of test compounds.…”

Section: Introductionmentioning

confidence: 99%

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

et al. 2004

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Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovo turkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using (32)P-postlabeling for DNA adducts. In ovo exposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had (32)P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity.

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“…One popular method is direct injection in ovo into the yolk, the albumen, or the air chamber. Test chemicals dissolved in water can be injected into the albumen through a small hole made on the eggshell [11]. Lipophilic chemicals can be introduced into the egg yolk [12].…”

Section: Discussionmentioning

confidence: 99%

Effects of diethylstilbestrol and ethinylestradiol on gene transcription of very low‐density apolipoprotein II in the liver of Japanese quail, Coturnix japonica

Hanafy

Sasanami

Mori

2006

Enviro Toxic and Chemistry

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Very low-density apolipoprotein II (apoVLDL) is one of the constituents of yolk in avian eggs. The expression of the apoVLDL gene is highly specific to the liver in mature female birds during the egg-laying period but is stimulated by exogenous estrogens in immature male birds. In the present study, we compared the effects of two estrogenic compounds, diethylstilbestrol and ethinylestradiol, on the expression of apoVLDL mRNA in the liver of Japanese quail (Coturnix japonica). Three-week-old, immature male quail were treated with a single intraperitoneal injection of the estrogenic compounds, and the level of apoVLDL mRNA in the liver was measured by gene-specific real-time polymerase chain reaction. Diethylstilbestrol and ethinylestradiol had a similar effect on the level of mRNA, increasing it in a dose-dependent manner. Next, the levels of apoVLDL mRNA in the liver of male embryos, which were developed in fertile eggs laid by quail injected with the estrogenic compounds during yolk formation, were measured. Maternal exposure to ethinylestradiol caused an increase in the mRNA in embryos, whereas exposure to diethylstilbestrol had no effect. These results point out the importance of the route of administration to the evaluation of the estrogenic effects of endocrine disruptors in oviparous species.

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In ovo carcinogenicity assay (IOCA): evaluation of mannitol, caprolactam and nitrosoproline

Cited by 13 publications

References 16 publications

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

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

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

Effects of diethylstilbestrol and ethinylestradiol on gene transcription of very low‐density apolipoprotein II in the liver of Japanese quail, Coturnix japonica

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