Rapid Induction of Preneoplastic Liver Foci in Embryonal Turkey Liver by Diethylnitrosamine

Enzmann, Harald; Kühlem, C.; Kaliner, G.; Löser, E.; Bannasch, Peter

doi:10.1177/019262339502300502

Cited by 12 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytological criteria for the diagnosis of LCD include cytoplasmic and nuclear changes, nuclear crowding or pleomorphism together with prominent nucleoli, hyperchromasia and sometimes multinucleation. The cytological features of liver cell dysplasia can strikingly mimic HCC 83 suggesting it is a putative preneoplastic lesion that can precede HCC in various species 1 , 10 , 41 , 45 , 84 , 85 , 86 , 87 . The precancerous nature of both LCC and SCC with regard to progression to HCC is somewhat controversial, but some claim that either one or both of them have been associated with development of HCC 31 , 35 , 38 , 49 , 82 , 87 , 88 , 89 , 90 .…”

Section: Discussionmentioning

confidence: 99%

Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

et al. 2012

View full text Add to dashboard Cite

In this comparative review, histomorphological features of common nonneoplastic and neoplastic hepatocyte lesions of rats and humans are examined using H&E-stained slides. The morphological similarities and differences of both neoplastic (hepatocellular carcinoma and hepatocellular adenoma) and presumptive preneoplastic lesions (large and small cell change in humans and foci of cellular alteration in rats) are presented and discussed. There are major similarities in the diagnostic features, growth patterns and behavior of both rat and human hepatocellular proliferative lesions and in the process of hepatocarcinogenesis. Further study of presumptive preneoplastic lesions in humans and rats should help to further define their role in progression to hepatocellular neoplasia in both species.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The IOCA has been proposed as a sensitive method for carcinogenicity testing, even when a single dose of test chemical is administered (Enzmann et al 1992(Enzmann et al , 1995. In chronic studies of DEN in rats (130 weeks), 1.35 mg/day DEN is required to induce hyperplastic nodules in the liver and 2.7 mg/day DEN per rat results in a statistically significant increase in hepatocellular carcinomas (Lijinsky et al 1981).…”

Section: Discussionmentioning

confidence: 99%

“…Within the last 15 years, the use of avian embryos has been proposed as rapid and inexpensive systems to study chemical-induced carcinogenesis by the induction of preneoplastic liver lesions (Hatch et al 1988;Enzmann et al 1992;Enzmann et al 1995). Such an in ovo carcinogenicity assay (IOCA) is not considered an animal model since experiments are terminated several days before hatching, and accordingly it can be performed in an ordinary laboratory setting (Enzmann and Brunnemann 1997;Enzmann et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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

Brunnemann

Enzmann

Perrone

et al. 2002

Archives of Toxicology

Self Cite

View full text Add to dashboard Cite

The in ovo carcinogenicity assay (IOCA) was used to examine whether the noncarcinogens epsilon-caprolactam (CAP), D-mannitol (MAN) and nitrosoproline (NPRO) induce toxicity and subsequently morphological changes in embryonic turkey livers compared with the carcinogen diethylnitrosamine (DEN). Various doses of the test compounds were injected into fertilized turkey or quail eggs prior to incubation. Embryonic livers were collected 3-4 days before hatching and processed for histology. The positive control DEN induced hepatocyte altered foci (HAF) and karyomegalic hepatocytes, whereas histological analysis of livers from embryos exposed to CAP, MAN and NPRO did not show such histological changes. The effects of the tested compounds on liver were further examined in hepatocytes cultured from exposed turkey and quail embryos. As observed in ovo, megalocytes as well as karyomegalic hepatocytes were present in hepatocyte cultures established from DEN-exposed turkey embryos, but not from embryos exposed to CAP, MAN or NPRO. It is concluded that CAP, MAN and NPRO do not induce histological changes in embryonic liver of the type produced by the carcinogen DEN, correlating with findings for these compounds in rodent studies.

show abstract

“…Exposure of turkey and quail embryos to the hepatocarcinogens diethylnitrosamine (DEN), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitroso-morpholine or urethane has been shown to induce foci of altered hepatocytes with morphologic and enzymatic characteristics of preneoplastic lesions observed in rodent liver (Enzmann et al 1992(Enzmann et al , 1995aEnzmann and Brunnemann 1997). Among other effects elicited in avian livers by nitrosamines are dose-dependent increases in nuclear size (Enzmann et al 1995b), a cellular response previously observed in rodents following exposure to low levels of hepatotoxicants and hepatocarcinogens (Carlson and Abraham 1985), which has been regarded as a mechanism involved in early stages of carcinogenesis Grasso 1985, 1987).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Rapid Induction of Preneoplastic Liver Foci in Embryonal Turkey Liver by Diethylnitrosamine

Cited by 12 publications

References 36 publications

Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

Comparative Histomorphological Review of Rat and Human Hepatocellular Proliferative Lesions

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

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

Contact Info

Product

Resources

About