Functional and proliferative effects of repeated low-dose oral administration of furan in rat liver

Molecular Nutrition and Food Research

Volumn 54, Issue 11, 2010, Pages 1556-1567

  Mally, Angela ^a   Graff, Carmen ^a   Schmal, Olga ^a   Moro, Sabrina ^a   Hamberger, Carolin ^a   Schauer, Ute M ^a   Brück, Jens ^b   Özden, Sibel ^a,e   Sieber, Max ^a   Steger, Ulrich ^a   Schrenk, Dieter ^b   Hard, Gordon C ^c   Chipman, James Kevin ^d   Dekant, Wolfgang ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b France   (Germany)

^c Private Consultant ^*  (New Zealand)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^e ISTANBUL UNIVERSITY   (Turkey)

Author keywords

Carcinogenicity; Cell proliferation; Furan; Liver

Indexed keywords

BILE ACID; CARCINOGEN; FURAN; FURAN DERIVATIVE;

ANIMAL; APOPTOSIS; ARTICLE; BLOOD; CARCINOGEN TESTING; CELL PROLIFERATION; DNA DAMAGE; FISCHER 344 RAT; LIVER; MALE; METABOLISM; METABOLOMICS; ORAL DRUG ADMINISTRATION; ORGAN SIZE; PATHOPHYSIOLOGY; RAT;

ADMINISTRATION, ORAL; ANIMALS; APOPTOSIS; BILE ACIDS AND SALTS; CARCINOGENICITY TESTS; CARCINOGENS, ENVIRONMENTAL; CELL PROLIFERATION; DNA DAMAGE; FURANS; LIVER; MALE; METABOLOMICS; ORGAN SIZE; RATS; RATS, INBRED F344;

RATTUS; RODENTIA;

EID: 77957143157     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201000064     Document Type: Article

References (29)

1. NTP, toxicology and carcinogenesis studies of furan (CAS No. 110-00-9) in F344 rats and B6C3F1 mice (gavage studies). Natl. Toxicol. Program Tech. Rep. Ser. 1993, 402, 1-286.
2. EFSA, Report of the Scientific Panel on Contaminants in the Food Chain on provisional findings on furan in food. The EFSA Journal 2004, 137, 1-20.
3. Chen, L. J., Hecht, S. S., Peterson, L. A., Identification of cis-2-butene-1, 4-dial as a microsomal metabolite of furan. Chem. Res. Toxicol. 1995, 8, 903-906.
4. Peterson, L. A., Naruko, K. C., Predecki, D. P., A reactive metabolite of furan, cis-2-butene-1, 4-dial, is mutagenic in the Ames assay. Chem. Res. Toxicol. 2000, 13, 531-534.
5. Byrns, M. C., Predecki, D. P., Peterson, L. A., Characterization of nucleoside adducts of cis-2-butene-1, 4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 2002, 15, 373-379.
6. Byrns, M. C., Vu, C. C., Peterson, L. A., The formation of substituted 1, N6-etheno-2'-deoxyadenosine and 1, N2-etheno-2'-deoxyguanosine adducts by cis-2-butene-1, 4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 2004, 17, 1607-1613.
7. Chen, L. J., Hecht, S. S., Peterson, L. A., Characterization of amino acid and glutathione adducts of cis-2-butene-1, 4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 1997, 10, 866-874.
8. Kellert, M., Brink, A., Richter, I., Schlatter, J., Lutz, W. K., Tests for genotoxicity and mutagenicity of furan and its metabolite cis-2-butene-1, 4-dial in L5178Y tk+/- mouse lymphoma cells. Mutat. Res. 2008, 657, 127-132.
9. Durling, L. J., Svensson, K., Abramsson-Zetterberg, L., Furan is not genotoxic in the micronucleus assay in vivo or in vitro. Toxicol. Lett. 2007, 169, 43-50.
10. Leopardi, P., Cordelli, E., Villani, P., Cremona, T. P. et al., Assessment of in vivo genotoxicity of the rodent carcinogen furan: evaluation of DNA damage and induction of micronuclei in mouse splenocytes. Mutagenesis 2010, 25, 57-62.
11. Wilson, D. M., Goldsworthy, T. L., Popp, J. A., Butterworth, B. E., Evaluation of genotoxicity, pathological lesions, and cell proliferation in livers of rats and mice treated with furan. Environ. Mol. Mutagen 1992, 19, 209-222.
12. Moser, G. J., Foley, J., Burnett, M., Goldsworthy, T. L., Maronpot, R., Furan-induced dose-response relationships for liver cytotoxicity, cell proliferation, and tumorigenicity (furan-induced liver tumorigenicity). Exp. Toxicol. Pathol. 2009, 61, 101-111.
13. Hickling, K. C., Hitchcock, J. M., Oreffo, V., Mally, A. et al., Evidence of oxidative stress and associated DNA damage, increased proliferative drive and altered gene expression in rat liver produced by the cholangiocarcinogenic agent furan. Toxicol. Pathol. 2010, 38, 230-243.
14. Hickling, K., Hitchcock, J. M., Chipman, J. K., Hammond, T. G., Evans, J. G., Induction and progression of cholangiofibrosis in rat liver injured by oral administration of furan. Toxicol. Pathol. 2010, 38, 213-229.
15. Mally, A., Volkel, W., Amberg, A., Kurz, M. et al., Functional, biochemical, and pathological effects of repeated oral administration of ochratoxin A to rats. Chem. Res. Toxicol. 2005, 18, 1242-1252.
16. Mally, A., Amberg, A., Hard, G. C., Dekant, W., Are 4-hydroxy-2(E)-nonenal derived mercapturic acids and (1)H NMR metabonomics potential biomarkers of chemically induced oxidative stress in the kidney? Toxicology 2007, 230, 244-255.
17. Sieber, M., Wagner, S., Rached, E., Amberg, A. et al., Metabonomic study of ochratoxin A toxicity after repeated administration: Phenotypic anchoring enhances ability for biomarker discovery. Chem. Res. Toxicol. 2009, 22 1221-1231.
18. Ando, M., Kaneko, T., Watanabe, R., Kikuchi, S. et al., High sensitive analysis of rat serum bile acids by liquid chromatography/electrospray ionization tandem mass spectrometry. J. Pharm. Biomed. Anal. 2006, 40, 1179-1186.
19. Lindon, J. C., Holmes, E., Nicholson, J. K., Metabonomics in pharmaceutical R&D. FEBS J. 2007, 274, 1140-1151.
20. Alden, C. L., Safety assessment for non-genotoxic rodent carcinogens: curves, low-dose extrapolations, and mechanisms in carcinogenesis. Hum. Exp. Toxicol. 2000, 19, 557-560; discussion 571-552.
21. Klaunig, J. E., Kamendulis, L. M., Xu, Y., Epigenetic mechanisms of chemical carcinogenesis. Hum. Exp. Toxicol. 2000, 19, 543-555.
22. Williams, G. M., Application of mode-of-action considerations in human cancer risk assessment. Toxicol. Lett. 2008, 180, 75-80.
23. Bai, C., Canfield, P. J., Stacey, N. H., Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury. Toxicology 1992, 75, 221-234.
24. Druckova, A., Mernaugh, R. L., Ham, A. J., Marnett, L. J., Identification of the protein targets of the reactive metabolite of teucrin A in vivo in the rat. Chem. Res. Toxicol. 2007, 20, 1393-1408.
25. Palmeira, C. M., Rolo, A. P., Mitochondrially-mediated toxicity of bile acids. Toxicology 2004, 203, 1-15.
26. Chen, T., Mally, A., Ozden, S., Dekant, W., Chipman J. K., Modulation of hepatic gene expression independent of DNA methylation in furan treated F344/N Rats. Society of Toxicology 48th Annual Meeting, Baltimore, 2009. The Toxicologist, Supplement to Toxicological Sciences 2009.
27. Maronpot, R. R., Giles, H. D., Dykes, D. J., Irwin, R. D., Furan-induced hepatic cholangiocarcinomas in Fischer 344 rats. Toxicol. Pathol. 1991, 19, 561-570.
28. Gill, S., Kavanagh, M., Bondy, G., Lefebvre, D. E. et al., Clinical and histopathologic effects of oral furan exposure in Fischer-344 rats. Toxicologist - J. Soc. Toxicol. 2008, 102.
29. Carthew, P., DiNovi, M., Setzer, R. W., Application of the margin of exposure (MoE) approach to substances in food that are genotoxic and carcinogenic: example: furan (CAS No. 110-00-9). Food Chem. Toxicol. 2010, 48, S69-S74.