473 1,2 1 2 2 (11 100193 ; 21, 100050) :,,,, :, ;; Progress in Rodent Models Used for Detecting the Allergenicity of Genetically Modified Foods SUN Na2na, PENG Yu2fa, J IA Xu2dong, Li Ning ( Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China) Abstract : With the rapid development of genetically modified ( GM) crops, a number of fundamental issues regarding health concerns have been raised. The potential allergenicity of GM foods is one of the focuses of attention. Recently, the development of animal models used for the assessment of allergenicity of GM crops has become a hot field of research and development. Several rodent models used for detecting the allergenicity of genetically modified foods were reviewed. Key words : Food, Genetically Modified ;Allergenicity Assessment ;Rodent Models Π, 1996,, 2S,, [1, 2 ],, [2 ], ( IFBC) ( ILSI) 1996 (decision tree approach) [3 ],2001 2003 (FAO) (WHO) [4, 5 ],, 1 (food allergy), :973 (2007CB109207) ; (2008ZX08011-005) : :, ( adverse reactions to food), (food intolerance) [6 ] 8 % 2 %4 % 315 kda IgE, [7 ], IgE I,,,CD4 + Th 2, IL24 IL213,Th 2 IL24 IL213 Th 1 IFN2 IL22 () IgE Th 2 (mast cell, MC) ( basophil, Bas) [8 ] IgE MC Bas,, IgE,,,,,, [9 ] CD8 + Tc
474 CHINESE JOURNAL OF FOOD HYGIENE 2009 21 5 IgE [8 ] 2 :, ;,, ; IgE Th 2 ; ; BALBΠc,C3HΠHeJ,,,, [10] 211 (Brown Norway, BN) BN (IgE),,BN,, BN, [11 ],BN, [12 ] [13-17 ], KNIPPELS [14 ] (OVA),( 0100220 mg OVA), () (,1 2,1 1,2 1 ) 42 BN OVA (1 mgπd),( ELISA) ( PCA), OVA IgE 80 % OVA IgE 2835, KNIPPELS [16 ] Wistar Piebald Virol Glaxo ( PVG) Hooded Lister (HL) BN OVA, BN OVA IgE, BN,KNIPPELS [15 ] BN BN OVA OVA BN, - ( 2lactoglobulin),,OVA OVA BN, BN [18 ] BN 1 mgπd OVA ( PAP) 10 mgπd (HEWP),BN OVA HEWP, PAP,BN [19 ] BN,,BN, 212 BALBΠc,BALBΠc,IgE, BN, Th 2 IgE [20, 21 ] DEARMAN [22, 23 ] BALBΠc, KIMBER [24 ] BALBΠc IgG IgE BALBΠc IgE ( inherent sensitizing potential), (immunogenic proteins) ( potentially allergenic proteins) IgG IgE,IgG IgE [22, 23, 25-27 ], : ( ) [8, 28 ], IgE,,,, BALBΠc DEARMAN [27, 29 ] 012 % 2 %OVA 20 % PAP 0125 ml
475 BALBΠc, PCA IgE,, 32 IgE ; OVA16 IgE ; PAP IgE,BALBΠ c [30 ] 2 %OVA (BSA) ( TI) PAP 0125 ml,,ova TI, BSA PAP BALBΠc,, BALBΠc IgE, 213 C3HΠHeJ C3HΠHeJ IgE, [31-33 ] BOWMAN [37 ] C3HΠHeJ BALBΠc,,, C3HΠHeJ,BALBΠc 68 C3HΠHeJ (food total protein), ( ),C3HΠHeJ [33, 34 ], +,TLR, IgE, [34 ] (1 mgπ 2 mgπ) + C3HΠHeJ Toll 4 ( Toll2like receptor 4, TLR4), (LPS) LI BASHIR [32, 35 ] TLR4 CAPOBIANCO [34 ] ( ST) + (cholera toxin, CT) 8 C3HΠHeJ mrna, IL213mRNA,IL24mRNA 5,IL24mRNA, IFN2 IL2 10,Th 2, ), [29 ], [31 ] LI [31, 32 ],,, 3 C3HΠHeJ (0101 011 110 2 mgπg BW) + CT ( 013g CTΠg BW), 5 C3HΠHeJ ( 1 mgπ, 5 mgπ ) + CT ( 10g CTΠ) 110 mgπg BW 1 mgπ PROUST [36 ], C3HΠHeJ, 4, 14 IgE, IgE, (10g CT), IgE,, IgE, IgE,, (5 mgπ+ 10g), IgE IgE, (,, [24 ],C3HΠHeJ
476 CHINESE JOURNAL OF FOOD HYGIENE 2009 21 5,, 3, BN,,BALBΠc, C3HΠHeJ Toll 4, C3HΠHeJ,, CT, [1 ] NORDLEEJ A, TAYLOR SL, TOWNSEND J A, et al. Identification of a Brazil2nut allergen in transgenic soybeans [J ]. N Engl J Med, 1996,334 (11) :6882692. [2 ] GOODMAN R E, VIETHS S, SAMPSON H A, et al. Allergenicity assessment of genetically modified crops what makes sense? [J ]. Nat Biotechnol, 2008, 26 (1) :73281. [3 ] METCALFE D D, ASTWOOD J D, TOWNSEND R, et al. Assessment of the allergenic potential of foods derived from genetically engineered crop plants[j ]. Crit Rev Food Sci Nutr, 1996, 36 Suppl : S1652186. [4 ] FAOΠWHO. Evaluation of allergenicity of genetically modified food. Report of a joint FAOΠWHO expert consultation on allergenicity of food derived from biotechnology[ R]. Rome :FAO, 2001. [5 ] FAOΠWHO. Codex alimentarius guideline for conduct of food safety assessment of foods derived from recombinant2dna plants ; Appendix IV : Annex on assessment of possible allergenicity. In Joint FAOΠWHO Food Standard Programme ( C. A. Commission, Ed. ) [ R]. Rome : Codex Alimentarius Commission, 2003. [6 ] BROSTOFF J. Food allergy and intolerance [J ]. Clin Exp Allergy, 1991, 21 Suppl 1 :3252329. [7 ] THOMAS K, HEROUET2GUICHENEY C, LADICS G, et al. Evaluating the effect of food processing on the potential human allergenicity of novel proteins : international workshop report[j ]. Food Chem Toxicol, 2007, 45 (7) :111621122. [8 ] KIMBER I, DEARMAN R J. Food allergy : what are the issues? [J ]. Toxicol Lett, 2001, 120 (123) :1652170. [9 ],,,. [J ].,2006, 31 (8) :125. [10 ] PRESCOTT V E, HOGAN S P. Genetically modified plants and food hypersensitivity diseases : usage and implications of experimental models for risk assessment[j ]. Pharmacol Ther, 2006, 111 (2) :3742 383. [11 ] KNIPPELS L M, PENNINKS A H. Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model[j ]. Environ Health Perspect, 2003, 111 (2) :2332238. [12 ] ATKINSON H A, JOHNSON I T, GEE J M, et al. Brown Norway rat model of food allergy : effect of plant components on the development of oral sensitization[j ]. Food Chem Toxicol, 1996, 34 (1) :27232. [13 ] KNIPPELS L M, PENNINKS A H, HOUBEN G F. Continued expression of anti2soy protein antibodies in rats bred on a soy protein2 free diet for one generation : the importance of dietary control in oral sensitization research[j ]. J Allergy Clin Immunol, 1998, 101 (6 Pt 1) :8152820. [14 ] KNIPPELS L M, PENNINKS A H, SPANHAAK S, et al. Oral sensitization to food proteins : a Brown Norway rat model [J ]. Clin Exp Allergy, 1998, 28 (3) :3682375. [15 ] KNIPPELS L M, PENNINKS A H, SMIT J J, et al. Immune2 mediated effects upon oral challenge of ovalbumin2sensitized Brown Norway rats : further characterization of a rat food allergy model [J ]. Toxicol Appl Pharmacol, 1999, 156 (3) :1612169. [16 ] KNIPPELS L M, PENNINKS A H, VAN MEETEREN M, et al. Humoral and cellular immune responses in different rat strains on oral exposure to ovalbumin[j ]. Food Chem Toxicol, 1999, 37 (8) :8812 888. [17 ] KNIPPELS L M, VAN DER KLEIJ H P, KOPPELMAN S J, et al. Comparison of antibody responses to hen s egg and cow s milk proteins in orally sensitized rats and food2allergic patients [ J ]. Allergy, 2000, 55 (3) :2512258. [18 ],,. Bn [J ]., 2005, 17 (2) :1032105. [19 ],,,. BN [J ]., 2004, 33 (1) :63265. [20 ] OKANO M, NISHIZAKI K, ABE M, et al. Strain2dependent induction of allergic rhinitis without adjuvant in mice [J ]. Allergy, 1999, 54 (6) :5932601. [21 ] RUSSO M, NAHORI M A, LEFORT J, et al. Suppression of asthma2like responses in different mouse strains by oral tolerance[j ]. Am J Respir Cell Mol Biol, 2001, 24 (5) :5182526. [22 ] DEARMAN R J, CADDICK H, BASKETTER D A, et al. Divergent antibody iso type responses induced in mice by systemic exposure to proteins : a comparison of ovalbumin with bovine serum albumin[j ]. Food Chem Toxicol, 2000, 38 (4) :3512360. [23 ] DEARMAN R J, CADDICK H, STONE S, et al. Characterization of antibody responses induced in rodents by exposure to food proteins : influence of route of exposure [J ]. Toxicology, 2001, 167 (3) :2172 231. [24 ] KIMBER I, DEARMAN R J, PENNINKS A H, et al. Assessment of protein allergenicity on the basis of immune reactivity : animal models [J ]. Environ Health Perspect, 2003, 111 (8) :112521130. [25 ] HILTON J, DEARMAN R J, BASKETTER D A, et al. Serological responses induced in mice by immunogenic proteins and by protein
477 respiratory allergens[j ]. Toxicol Lett, 1994, 73 (1) :43253. [26 ] HILTON J, DEARMAN R J, SATTAR N, et al. Characteristics of antibody responses induced in mice by protein allergens [J ]. Food Chem Toxicol, 1997, 35 (12) :120921218. [27 ] DEARMAN R J, KIMBER I. Determination of protein allergenicity : studies in mice[j ]. Toxicol Lett, 2001, 120 (123) :1812186. [28 ] HUBY R D, DEARMAN R J, KIMBER I. Why are some proteins allergens? [J ]. Toxicol Sci, 2000, 55 (2) :2352246. [29 ] DEARMAN R J, CADDICK H, STONE S, et al. Immunogenic properties of rapidly digested food proteins following gavage exposure of mice : a comparison of ovalbumin with a potato acid phosphatase preparation[j ]. Food Chem Toxicol, 2002, 40 (5) :6252633. [30 ],,,. BALB/ c [J ]., 2005, 34 (2) :2112213. [31 ] LI X M, SCHOFIELD B H, HUANG C K, et al. A murine model of IgE2mediated cows milk hypersensitivity [ J ]. J Allergy Clin Immunol, 1999, 103 (2 Pt 1) :2062214. [32 ] LI X M, SEREBRISKY D, LEE S Y, et al. A murine model of peanut anaphylaxis : T2and B2cell responses to a major peanut allergen mimic human responses[j ]. J Allergy Clin Immunol, 2000, 106 (1 Pt 1) :1502158. [33 ] MORAFO V, SRIVASTAVA K, HUANG C K, et al. Genetic susceptibility to food allergy is linked to differential TH22TH1 responses in C3HΠHeJ and BALBΠc mice [ J ]. J Allergy Clin Immunol, 2003, 111 (5) :112221128. [34 ] CAPOBIANCO F, BUTTERONI C, BARLETTA B, et al. Oral sensitization with shrimp tropomyosin induces in mice allergen2specific IgE, T cell response and systemic anaphylactic reactions [ J ]. Int Immunol, 2008, 20 (8) :107721086. [35 ] BASHIR M E, LOUIE S, SHI H N, et al. Toll2like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy [J ]. J Immunol, 2004, 172 (11) :697826987. [36 ] PROUST B, ASTIER C, JACQUENET S, et al. A single oral sensitization to peanut without adjuvant leads to anaphylaxis in mice [J ]. Int Arch Allergy Immunol, 2008, 146 (3) :2122218. [37 ] BOWMAN C C, SELGRADE M K. Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility : potential approaches to safety assessment [J ]. Toxicol Sci, 2008, 102 (1) :1002109. [ :2009-03 - 10 ] :R15 ;Q788 ;TS20116 :E :1004-8456 (2009) 05-0473 - 05 (2009 6 ),,,,,,:, 2009 6 30,,,,,,