• Toxicological Research
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• v.11 no.1
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• pp.77-80
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• 1995

Antigenic potential of genetically-engineered human erythropoietin (EPO) was assessed in guinea pigs (active systemic anaphylaxis [ASA] ; passive cutaneous anaphylaxis [PCA]) and in vitro (hemagglutination test [PHA]). In ASA, EPO at 70~700 U/kg elicited a weak anaphylactic response tvhereas the positive control ovalbumin (OVA) did cause intensive responses leading to death in 40% animals. However, the extract of CHO cells, to which EPO gene was introduced, did not cause any symptom. In PCA and PHA tests, neither EPO nor CHO cell extract induced positive responses. OVA, in contrast, produced high titers in both PCA and PHA tests. It was concluded that, in light of the fact that EPO was slightly antigenic only in ASA but not in PCA or PHA and also that human EPO is a foreign protein to guinea pigs, the present EPO may not be antigenic in humans.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.236-243
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• 1993

Immunologic potential of DA-125, a new anthracycline antitumor antibiotic, was investigated using guinea pigs and mice. In antigenicity experiments, guinea pigs were sensitized subcutaneously with DA-125 or DA-125 incorporated in complete Freund's adjuvant (CFA) once a week for three weeks. No systemic anaphylaxis was induced by intravenous injection of DA-125 or DA-125 incubated with guinea pig serum after 3 weeks from the last sensitization. None of sera of these animals showed any passive cutaneous anaphylactic reaction (PCA) when DA-125 or DA-125 incubated with guinea pig serum was used as a challenging antigen in homologous PCA experiment. On the other hand the treatment of guinea pigs with ovalbumin Incorporated in CFA induced systemic anaphylactic reaction when challenged by intravenous injection of 5 mg/body of ovalbumin. Immunodiffusion test revealed no precipitating antibodies as detected in guinea pigs sensitized with DA-125. In 24-hour heterologous PCA reaction with sera of C57BL/6 mice immunized with DA-125 or DA-125 mixed with aluminum hydroxide gel (Alum), None of sera showed positive reaction when DA-125 or DA-125 incubated with rat serum was used as a challenging antigen. Sera of animals immunized with a mixture of ovalbumin and alum showed positive PCA reaction when 5 mg/body of ovalbumin was injected as a challenging antigen. In lymphocyte proliferation tests, spleen lymphocyte proliferation to PHA and LPS was similarly impaired by 12 mg/kg of DXR or 36 mg/kg of DA-125, and the immunodepressive activity of DA-125 showed a dose-dependent manner. From these results, it could be concluded that immunosupression of DA-125 would be comparable to that of DXR and that DA-125 would not induce systemic allergic reaction in its clinical use.

• Journal of Pharmacopuncture
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• v.14 no.4
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• pp.23-32
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• 2011

Objectives: This study was performed to examine the antigenic potential of pure melittin (Sweet Bee Venom - SBV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), authorized a non-clinical studies institution, under the regulations of Good Laboratory Practice (GLP). Antigenic potential of SBV was examined by active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) in guinea pigs. SBV was subcutaneously administered at 0.07 and 0.28mg/kg and also as a suspension with adjuvant (Freund's complete adjuvant: FCA). Ovalbumin (OVA) as a suspension with adjuvant was used to induce positive control response ($5mg/m{\ell}$-FCA). Results: 1. In the ASA test, experimental groups showed some symptoms of anaphylaxis like piloerection, hyperpnea and staggering gait. 2. In the PCA test, low dosage group did not show any antibody responses, whereas high dosage group showed positive responses. 3. In the weight measurement and clinical observation, experimental groups didn't show any significant changes compared with control group. 4. In the autopsy of body, the abnormalities of lung were detected in the corpse. This means that the cause of death may induced anaphylactic shock. Conclusions: Above findings suggested that SBV had antigenic potential in guinea pig. Further studies on the subject should be conducted to yield more concrete evidences.

• Toxicological Research
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• v.8 no.2
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• pp.255-263
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• 1992

SKI 2053R and SKI 2053R-human serum albumin(HSA) mixture were examined for their antigenicity in Hartley guinea pigs as well as C57BL/6 mice in comparison with distilled water (DW), HSA and DW-HSA conjugate. Several antigenicity tests, including acitive systemic anaphylaxis(ASA), passive systemic anaphylaxis (PSA), passive cutaneous anaphylaxis (PCA) and indirect hamagglutination test (IHA), were performed according to the Established Regulations of National Institute of Safety Research. The results were as follows: 1. When guinea pigs were sensitized with SKI2053R or SKI2053R-HSA emulsified with complete Freund's adjuvant(CFA), these animals showed negative reactions in ASA and PSA. 2.No blue spot was observed on the back skin of guinea pigs in the PCA test. 3. Sera from guinea pigs revealed a negative reaction in IHA. 4.Guinea pigs were sensitized by HSA emulsified with CFA as a positive control, and these animals showed positive reactions in ASA, PSA, PCA, and IHA. As shown above, SKI2053R was considered to possess neither antigenic, nor haptenic properties, and confirmed not to have the haemagglutinating activity.

• Toxicological Research
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• v.8 no.1
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• pp.17-27
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• 1992

Antigenicity of Recombinant Granulocyte macrophage colony stimulating factor(LBD-005), a newly developed drug for hematopoietic growth, was investigated in mice and guinea pigs. 1. Mice showed production of antibodies against LBD-005 (100mg/kg) with alumin]m hydroxide gel(alum) as an adjuvant, judged by the heterologous anaphylaxis(PCA) test using rats. On the other hand, antibodies against ovalbumin(OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-005 only and of LBD-005 with complete Freund's adjuvant(CFA) as an adjuvant did not produce positive reactions in homologous passive cutaneous anaphylaxis (PCA).

• Toxicological Research
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• v.9 no.1
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• pp.125-132
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• 1993

Antigenic potential of recombinant human growth hormone (LBD-007), a newly developed drug for growth hormone deficiency, was investigated in mice and guinea pigs. 1. Mice showed production of antibodies against LBD-009 (1.5IU/kg) with aluminum hydroxide gel(alum) as an adjuvant, Judaged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-009 (0.15IU/kg-1.5IU/kg) only and of LBD-009 with complete Freund's adjuvant (CFA) as an adjuvant did produce weak positive reactions in homologous passive cutaneous anaphylaxis (PCA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in PCA.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.255-261
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• 2003

The antigenicity of nonspecific immunostimulator BARODON$^{(R)}$, a newly developed drug, was investigated by tests for passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mice and guinea pigs. In ASA test using guinea pigs, there were no significant clinical symptoms in all individuals of low(0.3%) and high(3%) dose of both groups treated with only BARODON$^{(R)}$ and cotreated with BARODON$^{(R)}$ and adjuvant group. In PCA test, blue spots of Evan's were observed from $2^6$ to $2^{10}$ in homologous group and from $2^2{\sim}2^5$ dilution rate in heterologous group of BSA treated positive control group. However, intradermal sensitization with antiserum obtained from low (0.3%) and high (3%) dose of BARODON$^{(R)}$ only treatment group and treated-with-adjuvant group, followed by intravenous injection of respective antigen and Evan's blue mixture (1:1) showed no blue spot observed. In conclusion, BARODON$^{(R)}$, as showed in ASA and PCA test, did not cause anaphylatic shock when treated 3 and 10 times higher than clinically intended dose, nor induce IgE, so that might not have antigenic properties in mice and guinea pigs.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.48-52
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• 1997

The antigenic potential of CFA-001, cefazolin, a cephalosporin derivative produced by an enzy-matic semisynthesis, was determined in Hartley guinea pigs. A battery of tests employed consisted of active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA), and indirect hemagglutination test (IHA). The results were as follows: 1) In ASA, no signs attributable to anaphylaxis was observed in guinea pigs sensitized with CFA-001, whereas OVA-sensitized animals induced severe anaphylactic symptoms; 2) guinea pigs did not produce antibodies against CFA-001 when sensitized with or without Freund's complete adjuvant (FCA) in homologous PCA tests. Meanwhile, antibodies against ovalbumin (OVA) were clearly detected; 3) No CFA-001-specific hemagglutination was observed in the IHA using sera obtained from CFA-001- sensitized guinea pigs. These results suggest that CFA-001 has no antigenicity potential in guinea pigs.

• Archives of Pharmacal Research
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• v.24 no.3
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• pp.256-261
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• 2001

Allergenicity of genetically-modified (GM) soybean was evaluated in male Sprague Dawley rats. To confirm the GM soybean used in this study, the polymerase chain reaction (PCR) was performed using the chromosomal DNA of soybeans. The PCR result provided the clear discrimination of genetically-modified (GM) soybeans. To evaluate the allergenicity of GM soybean and non-GM control one, the soybean homogenate was sensitized subcutaneously 3 times a week for 3 weeks. The doses of soybean were 0, 2 and 20 mg/kg in the protein basis. A week after the last sensitization, antisera were recovered from individual animals. When the sera were injected intradermally on the clipped back of unsensitized rats with various dilutions, followed by a challenge with 20 mg/kg of soybean homogenate containing 1% Evans blue, no sign of passive cutaneous anaphylaxis reaction was detected. In addition, when the sera were treated in the cultures of peritoneal mast cells, the increase of histamine release by anti-(GM soybean) sera was not observed when compared to that by anti-(non-GM soybean) sera. The present results indicate that the GM soybean might not act as a strong allergen in male Sprague Dawley rats.