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

Perrone, Carmen E.; Ahr, Hans-Juergen; Duan, Jian Dong; Jeffrey, Alan M.; Schmidt, Ulrich; Williams, Gary M.; Enzmann, H.

doi:10.1007/s00204-004-0580-1

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…Consistent with studies in hatched poultry, turkeys may be more sensitive to embryotoxic effects than chickens [215]. Since embryonic liver has an active protein from the CYP1A family [216], hepatotoxicity in turkey embryos is likely mediated by the same P450 1A5 as in poults.…”

Section: Embryotoxicitysupporting

confidence: 58%

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

2015

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This review is a comprehensive introduction to the effects of poultry exposure to the toxic and carcinogenic mycotoxin aflatoxin B1 (AFB1). The relationship between AFB1 sensitivity and metabolism, major direct and indirect effects of AFB1, recent studies of gene expression and transcriptome responses to exposure, and mitigation strategies to reduce toxicity are discussed. Exposure to AFB1 primarily occurs by consumption of contaminated corn, grain or other feed components. Low levels of residual AFB1 in poultry feeds can cause reduction in growth, feed conversion, egg production, and compromised immune functions, resulting in significant economic costs to producers. Thus, AFB1 acts as a "force multiplier" synergizing the adverse effects of microbial pathogens and other agents, and factors detrimental to poultry health. Domestic turkeys (Meleagris gallopavo) are one of the most sensitive animals known to AFB1 due, in large part, to a combination of efficient hepatic bioactivation by cytochromes P450 1A5 and 3A37, and deficient hepatic glutathione-S-transferase (GST)-mediated detoxification. Because of their sensitivity, turkeys are a good model to investigate chemopreventive treatments and feed additives for their ability to reduce AFB1 toxicity. Transcriptome analysis (RNA-seq) of turkey poults (liver and spleen) has identified AFB1-induced gene expression changes in pathways of apoptosis, carcinogenesis, lipid regulation, antimicrobial activity, cytotoxicity and antigen presentation. Current research focuses on further identifying the molecular mechanisms OPEN ACCESSAgriculture 2015, 5 743 underlying AFB1 toxicity with the goal of reducing aflatoxicosis and improving poultry health.

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Section: Embryotoxicitysupporting

confidence: 58%

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

2015

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“…Rather post-translational modifications may be responsible for the inactivity of GSTAs against AFBO in domesticated turkeys [ 8 ]. It is important to note that while hepatic GST enzymes are produced in turkey embryos [ 62 ]; their AFB 1 -conjugating activity has not been examined. Furthermore, since AFB 1 exposure can lead to oxidative stress and lipid peroxidation [ 63 , 64 , 65 ], up-regulation of GSTA genes may reflect antioxidant functions of glutathione instead of AFBO detoxification.…”

Section: Discussionmentioning

confidence: 99%

“…The activity of hepatic P450 enzymes and therefore AFB 1 sensitivity is inversely related to age in turkey poults [ 1 , 34 , 69 , 76 ]. An active protein from the CYP1A family has been identified in embryonic liver [ 62 ], suggesting that hepatotoxicity in turkey embryos may also be driven by P450 1A5. In this study, decreased expression of CYP1A5 over time may indicate that domesticated turkeys are more susceptible to toxicity earlier in development.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Transcriptome Responses of Domesticated and Wild Turkey Embryos to Aflatoxin B1

Monson

Cardona

Coulombe

et al. 2016

Toxins

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The mycotoxin, aflatoxin B1 (AFB1) is a hepatotoxic, immunotoxic, and mutagenic contaminant of food and animal feeds. In poultry, AFB1 can be maternally transferred to embryonated eggs, affecting development, viability and performance after hatch. Domesticated turkeys (Meleagris gallopavo) are especially sensitive to aflatoxicosis, while Eastern wild turkeys (M. g. silvestris) are likely more resistant. In ovo exposure provided a controlled AFB1 challenge and comparison of domesticated and wild turkeys. Gene expression responses to AFB1 in the embryonic hepatic transcriptome were examined using RNA-sequencing (RNA-seq). Eggs were injected with AFB1 (1 μg) or sham control and dissected for liver tissue after 1 day or 5 days of exposure. Libraries from domesticated turkey (n = 24) and wild turkey (n = 15) produced 89.2 Gb of sequence. Approximately 670 M reads were mapped to a turkey gene set. Differential expression analysis identified 1535 significant genes with |log2 fold change| ≥ 1.0 in at least one pair-wise comparison. AFB1 effects were dependent on exposure time and turkey type, occurred more rapidly in domesticated turkeys, and led to notable up-regulation in cell cycle regulators, NRF2-mediated response genes and coagulation factors. Further investigation of NRF2-response genes may identify targets to improve poultry resistance.

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“…All rights reserved. For permissions, please email: journals.permissions@oup.com also as demonstrated in other systems, including the turkey fetal liver (Perrone et al, 2004). Fetal chicken egg livers were shown to be similar in susceptibility to aflatoxin B 1 (AFB 1 ) induction of DNA breaks using the comet assay compared with that of the turkey egg fetal liver (Williams et al, 2011b).…”

mentioning

confidence: 71%

“…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%

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

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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.

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

Cited by 19 publications

References 43 publications

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Hepatic Transcriptome Responses of Domesticated and Wild Turkey Embryos to Aflatoxin B1

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

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