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Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

Nan Mei, Lei Guo, Ruqing Liu, James C Fuscoe, Tao Chen
2007 BMC Bioinformatics  
Results: Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined.  ...  Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study.  ...  Riddelliine also produced a unique mutational spectrum in the liver cII gene of Big Blue rats with G:C → T:A transversions being the major type of mutation [14] .  ... 
doi:10.1186/1471-2105-8-s7-s4 pmid:18047727 pmcid:PMC2099496 fatcat:cak4l2yi7jaadj4apa5oj6lk2u

Genotoxicity of pyrrolizidine alkaloids

Tao Chen, Nan Mei, Peter P. Fu
2010 Journal of Applied Toxicology  
PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors.  ...  Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants aff ecting livestock and wildlife.  ...  the types of mutations in cII gene from riddelliine-or comfrey-treated and control Big Blue rats Type of mutation Control (%) Treatment (%) In liver In lung Riddelliine in liver Comfrey in liver  ... 
doi:10.1002/jat.1504 pmid:20112250 fatcat:lvveellxvbdurfgaoawbdkkpby

Metabolism, Genotoxicity, annd Carcinogenicity of Comfrey

Nan Mei, Lei Guo, Peter P. Fu, James C. Fuscoe, Yang Luan, Tao Chen
2010 Journal of Toxicology and Environmental Health. Part B, Critical Reviews  
The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development  ...  Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.  ...  The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration.  ... 
doi:10.1080/10937404.2010.509013 pmid:21170807 pmcid:PMC5894094 fatcat:bb76fh7s55gdlf4yol46hquhbm

Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver

Lei Guo, Nan Mei, Stacey Dial, James Fuscoe, Tao Chen
2007 BMC Bioinformatics  
Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals.  ...  Results: Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks.  ...  Acknowledgements The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration.  ... 
doi:10.1186/1471-2105-8-s7-s22 pmid:18047722 pmcid:PMC2099491 fatcat:pwftjbexujaelaubwqq2gqcbsm

Gene Expression Profiling as an Initial Approach for Mechanistic Studies of Toxicity and Tumorigenicity of Herbal Plants and Herbal Dietary Supplements

Lei Guo, Nan Mei, Qingsu Xia, Tao Chen, Po-Chuen Chan, Peter P. Fu
2010 Journal of Environmental Science And Health Part C - Environmental Carcinogenesis & Ecotoxicology Reviews  
The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement.  ...  Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs  ...  This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.  ... 
doi:10.1080/10590500903585416 pmid:20390968 pmcid:PMC5736312 fatcat:vxydf4vbubgwjg53vrngdfmhh4

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

Yisheng He, Lin Zhu, Jiang Ma, Ge Lin
2021 Archives of Toxicology  
Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species.  ...  In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.  ...  Acknowledgements The work was supported by Research Grants Council of Hong Kong Special Administrative Region (GRF Project nos. 14111816, 14106318, 14107719 and 14106120).  ... 
doi:10.1007/s00204-021-03060-w pmid:34003343 fatcat:yjstnsdokvfablddn2f7un3orq

Analysis of gene expression changes in relation to toxicity and tumorigenesis in the livers of Big Blue transgenic rats fed comfrey (Symphytum officinale)

Nan Mei, Lei Guo, Lu Zhang, Leming Shi, Yongming Sun, Chris Fung, Carrie L Moland, Stacey L Dial, James C Fuscoe, Tao Chen
2006 BMC Bioinformatics  
Results: In this study, we identified comfrey-induced gene expression profile in the livers of rats.  ...  Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in  ...  The views presented in this article do not necessarily reflect those of the Food and Drug Administration.  ... 
doi:10.1186/1471-2105-7-s2-s16 pmid:17118137 pmcid:PMC1683566 fatcat:ha6murdphfd7dj3y7k2wasvjom

Analysis of in vivo mutation data can inform cancer risk assessment

Martha M. Moore, Robert H. Heflich, Lynne T. Haber, Bruce C. Allen, Annette M. Shipp, Ralph L. Kodell
2008 Regulatory toxicology and pharmacology  
Our analysis of published data on riddelliine in rats and dichloroacetic acid in mice indicates that our approach has merit.  ...  We are currently evaluating whether the analysis of in vivo gene mutation data can inform the risk assessment process by better defining the MOA for cancer and thus influencing the choice of the low-dose  ...  Acknowledgement: The authors would like to acknowledge Michael L. Dourson for his significant participation and contributions during the development of the concepts described in this paper.  ... 
doi:10.1016/j.yrtph.2008.01.015 pmid:18321622 fatcat:5v2qbc6xevfivnasozg23yzczq

Scientific Opinion on Pyrrolizidine alkaloids in food and feed

2011 EFSA Journal  
The European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on pyrrolizidine alkaloids (PA) in food and feed.  ...  A benchmark dose lower confidence limit for a 10 % excess cancer risk (BMDL 10 ) of 70 µg/kg b.w. per day for induction of liver haemangiosarcomas by lasiocarpine in male rats was calculated as the reference  ...  Mutations induced by riddelliine were also found in K-ras and p53 genes in liver hemangiosarcomas in B6C3F1 mice (Hong et al., 2003) .  ... 
doi:10.2903/j.efsa.2011.2406 fatcat:hwi42gflrzfbhdvdxnqypan7ym

A foresight study on emerging technologies: State of the art of Omics technologies and potential applications in food and feed safety

A Pielaat, GC Barker, P Hendriksen, P Hollman, A Peijnenburg, BH Ter Kuile
2013 EFSA Supporting Publications  
A foresight study on emerging technologies: State of the art of omics technologies and potential applications in food and feed safety Pielaat, A.; Barker, G.C.; Hendriksen, P.; Peijnenburg, A.; ter Kuile  ...  Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats.  ...  Results of the omics experiments Mei et al (2007) studied gene expression in livers of female Big Blue transgenic rats upon oral gavage at a dose of 1 mg/kg body weight riddelliine 5 days a week for 12  ... 
doi:10.2903/sp.efsa.2013.en-495 fatcat:p62tnrhkuzfmpewkoukfjc3fba

Mode of action-based risk assessment of genotoxic carcinogens

Andrea Hartwig, Michael Arand, Bernd Epe, Sabine Guth, Gunnar Jahnke, Alfonso Lampen, Hans-Jörg Martus, Bernhard Monien, Ivonne M C M Rietjens, Simone Schmitz-Spanke, Gerlinde Schriever-Schwemmer, Pablo Steinberg (+1 others)
2020
alkaloids.  ...  alkaloids.  ...  The authors would like to thank all members and guests of the SKLM and MAK Commission for critical reading of the manuscript and helpful suggestions.  ... 
doi:10.5167/uzh-195997 fatcat:xqzkmgoeqvcilbqyzurdjbasvm

Mode of action-based risk assessment of genotoxic carcinogens

Andrea Hartwig, Michael Arand, Bernd Epe, Sabine Guth, Gunnar Jahnke, Alfonso Lampen, Hans-Jörg Martus, Bernhard Monien, Ivonne M. C. M. Rietjens, Simone Schmitz-Spanke, Gerlinde Schriever-Schwemmer, Pablo Steinberg (+1 others)
2020
alkaloids.  ...  (threshold levels) in case of the latter group.  ...  The authors would like to thank all members and guests of the SKLM and MAK Commission for critical reading of the manuscript and helpful suggestions.  ... 
doi:10.5445/ir/1000121452 fatcat:xd4txll53vezvhphxupp6pnrre

Veterinary Drug Residues in Foods [chapter]

Els Daeseleire, Els Van Pamel, Christof Van Poucke, Siska Croubels
2017 Chemical Contaminants and Residues in Food  
However, the transfer of fluoride to the edible part of the fish is low (Julshamn et al., 2004b; Moren et al., 2007; Hansen et al., 2012) , whereas krill meale derived fluoride can accumulate in liver  ...  Chemical contaminants in the substrate may accumulate in insects; however, there is a lack of data on the nature and extent of accumulation of these in insects.  ...  Mutation frequencies induced by PhIP in the lacI gene of the colon of Big Blue mice and Big Blue rats were similar, but there was a higher incidence of GC / TA transversions in the rats.  ... 
doi:10.1016/b978-0-08-100674-0.00006-0 fatcat:hojpttum7jbbzm5ldt6dkcxblm