[표제지 등]

제출문

요약문

SUMMARY

칼라

List of Table

List of Figure

List of Table

List of Figure

List of Table

List of Figure

List of Table

List of Figure

목차

In vitro 독성시험법 개발에 관한 연구 50

제출문 52

요약문 53

SUMMARY 65

목차(제목없음) 78

In vitro 표적장기독성시험법 개발에 관한 연구 78

제출문 79

요약문 80

SUMMARY 87

목차 94

제1장 서론 98

제2장 국내외 기술개발 현황 105

제3장 연구개발수행 내용 및 결과 109

제1절 In vitro 간장독성 시험법 개발 109

제2절 In vitro 신경독성 시험법 개발 121

제3절 In vitro 신장독성 시험법 개발 129

제4장 연구개발목표 달성도 및 대외기여도 142

제5장 연구개발결과의 활용 계획 146

제6장 참고 문헌 147

부록 : In vitro 표적장기독성시험법의 표준작업 지침서 179

In vitro 국소독성시험법 개발에 관한 연구 202

제출문 203

요약문 204

SUMMARY 209

목차 213

제1장 서론 221

제2장 국내외 기술개발 현황 224

제3장 연구개발수행내용 및 결과 225

제1절 시료 225

제2절 시험방법 228

1. In vitro 시험 228

2. In vivo 시험 231

제3절 결과 분석 234

제4절 결과 234

제5절 고찰 241

제4장 연구개발목표 달성도 및 대외기여도 243

제5장 연구개발결과의 활용계획 244

제6장 참고문헌 244

감사의 글 250

In vitro 생식독성시험법 개발에 관한 연구 290

제출문 291

요약문 292

SUMMARY 295

목차 298

제1장 서론 300

제2장 국내외 기술개발 현황 303

제3장 연구개발수행 내용 및 결과 306

제1절 흰쥐 배자 중뇌세포에 미치는 all trans-retinoic acid의 독성 306

제2절 배지 중 혈청이 흰쥐 배자 중뇌세포의 증식과 분화에 미치는 영향 326

제3절 배지 중 혈청이 흰쥐 배자 지아세포의 증식과 분화에 미치는 영향 344

제4절 Phenylalanine 및 그 유사물질과 항산화물질들이 흰쥐 배자의 중뇌세포에 대한 ochratoxin A의 독성에 미치는 영향 359

제5절／제6절 In vitro battery 생식독성시험법에 의한 중금속의 독성 검색 378

제4장 연구개발목표 달성도 및 대외기여도 424

제5장 연구개발결과의 활용계획 425

제6장 참고문헌 426

부록. In vitro 생식독성시험법의 표준작업지침서 443

In vitro 유전독성시험법 개발에 관한 연구 470

제출문 471

요약문 472

SUMMARY 477

목차 482

제1장 서론 486

제2장 국내외 기술개발 현황 489

제3장 연구개발수행내용 및 결과 490

제1절 실험재료(시험물질) 490

제2절 시험방법 493

1. 포유류 배양세포를 이용한 유전자 돌연변이 시험법 493

2. 단세포 전기영동 시험법 496

3. 염색체이상시험 498

4. 소핵시험 500

제3절 실험 결과 503

1. 포유류 배양세포를 이용한 유전자 돌연변이 시험법 503

2. 단세포 전기영동 시험법 506

3. 염색체이상시험 507

4. 소핵시험 508

제4절 고찰 510

제5절 결론 513

제4장 연구개발목표 달성도 및 대외기여도 515

제5장 연구개발결과의 활용계획 516

제6장 참고문헌 517

부록 : 표준작업지침서(제목없음) 539

In vitro 광독성시험법 개발에 관한 연구 554

제출문 555

요약문 556

SUMMARY 560

목차 564

제1장 서론 574

제2장 국내외 기술개발 현황 582

제3장 연구개발수행 내용, 결과 및 고찰 584

제1절 연구개발수행 내용 584

제2절 연구결과 594

제3절 고찰 611

제4장 연구개발목표 달성도 및 대외기여도 622

제5장 연구개발결과의 활용계획 624

제6장 참고문헌 625

부록 1. In vitro 광독성시험법 표준작업 지침서 706

암전이 관련 효소를 이용한 새로운 암전이 억제제 검색법 확립 717

제출문 718

요약문 719

SUMMARY 723

목차 727

제1장 서론 729

제2장 국내외 기술 개발 현황 735

제3장 연구 개발 수행 내용 및 결과 736

제1절 연구 내용 및 방법 736

1. In vitro 암전이 시험법 확립 736

2. In vitro 암전이 억제물질의 검색 738

3. In vivo 암전이 시험법 확립 739

4. Spontaneous metastasis 관련 유전자 동정 739

5. Yakuchinone A 및 B에 의한 암전이 및 발암촉진 억제작용의 검토 741

제2절 연구결과 743

1. In vitro 암전이 시험법 확립 743

2. In vitro 암전이 억제물질의 검색 745

3. In vivo 암전이 시험법 746

4. Spontaneous metastasis 관련 유전자 동정 747

5. Yakuchinone A와 B에 의한 암전이와 발암 억제작용 검토 748

*도표 및 그림들(제목없음) 751

제4장 연구 개발 목표 달성도 및 대외 기여도 800

제5장 연구 개발 결과의 활용 계획 801

제6장 참고문헌 802

[건강식품의 암전이 억제 검색에 관한 연구] 806

제출문 807

요약문 808

SUMMARY 811

목차 813

제1장 서론 815

제2장 실험방법 822

1. 개요 822

2. 시료의 선정 822

3. 시료의 추출 825

4. 세포주 및 배양조건 825

5. 세포주에 대한 각 시험물질의 성장 저해 효과 및 적정농도 설정 실험 825

6. MMP9P-SEAP의 유전자 발현 억제물질 탐색 828

7. Gel- zymogram을 이용한 MMP-9 및 MMP-2 gelatinase 의 활성 측정 829

제3장 연구결과 830

1. 시료의 선정 830

2. 시료 추출물의 제조 830

3. 세포주에 대한 각 시험물질의 성장저해 효과 및 적정 농도 설정 830

4. MMP9P-SEAP의 유전자 발현 억제물질 탐색 835

5. Gel-zymogram을 이용한 MMP-9 gelatinase 및 MMP-2 gelatinase의 in-vivo activity 측정 835

제4장 결론 847

제5장／제6장 참고문헌 849

생체내 중기 발암성 시험법 연구 851

제출문 852

요약문 853

Summary862

목차 871

제1장 서론 873

제2장 국내외 기술개발 현황 878

제3장 연구개발 수행내용 및 결과 881

제1절 실험방법 881

1. 1차년도 (실험 I) 881

2. 2차년도 (실험 II) 885

3. 3차년도 (실험 III) 888

제2절 결과 891

1. 1차년도 (실험 I) 891

2. 2차년도 (실험 II) 897

3. 3차년도 (실험 III) 902

4. Legends for figures 907

제3절 고찰 912

제4장 연구개발목표달성도 및 대외기여도 920

제5장 연구개발결과의 활용계획 921

제6장 참고문헌 922

Contents(제목없음)

[Studies on the Development of In vitro Toxicity Tests etc.] 50

SUMMARY 65

Contents 78

[Development of In vitro Target Organ Toxicity Test etc.] 78

SUMMARY 87

Contents 95

Chapter 1. Introduction 98

Chapter 2. Current status of method development 105

Chapter 3. Experimental methods & Results 109

Section 1. In vitro Hepatotoxicity test 109

Section 2. In vitro Neurotoxicity test 121

Section 3. In vitro Nephrotoxicity test 129

Chapter 4. Achievements & Contributions 142

Chapter 5. Plan for practical use of results 146

Chapter 6. References 147

Appendix. Standard Operating(Operationg) Procedures 179

[Development of In vitro Local toxicity Test etc.] 202

SUMMARY 209

Contents 214

Chapter 1. Introduction 221

Chapter 2. Current status of method development 224

Chapter 3. Experimental methods & Results 225

Section 1. Test compound 225

Section 2. Methods 228

1. In vitro test 228

2. In vivo test 231

Section 3. Statistics 234

Section 4. Results 234

Section 5. Discussion 241

Chapter 4. Achievements & Contributions 243

Chapter 5. Plan for practical use of results 244

Chapter 6. References 244

Acknowledgements(Acknowlegements) 250

[Development of In vitro Reproductive and Developmental toxicity tests etc.] 290

SUMMARY 295

Contents 299

Chapter 1. Introduction 300

Chapter 2. Current Status of Method Development 303

Chapter 3. Experimental Methods and Results 306

Section 1. Toxic effects of all trans-retinoic acid in rat embryonic midbrain cells micromass culture 306

Section 2. Differential effects of sera on basal and chemical-induced cell proliferation and differentiation in rat embryonic midbrain cells micromass culture 326

Section 3. Differential effects of sera on basal and chemical-induced cell proliferation and differentiation in rat embryonic limb bud cells micromass culture 344

Section 4. Ochratoxin A-induced embryo toxicity and preventive effect of several substances in cultured rat embryonic midbrain cells 359

Section 5. Teratogenic potential of heavy metals in in vitro battery teratogenicity test system 378

Chapter 4. Achievement and Contribution 424

Chapter 5. Application of the Results 425

Chapter 6. References 426

Appendix. Standard operating procedure (SOP) of in vitro battery teratogenicity test system 443

[Development of In vitro Genetic Toxicity Tests etc.] 470

SUMMARY 477

Contents 483

Chapter 1. Introduction 486

Chapter 2. Current status of method development 489

Chapter 3. Experimental methods & Results 490

Section 1. Experimental materials 490

Section 2. methods 493

1. Mouse lymphoma tk gene mutation assay 493

2. Single cell gel electrophoresis 496

3. In vitro Chromosome aberration test 498

4. In vivo Micronucleus test 500

Section 3. Results 503

1. Mouse lymphoma tk gene mutation assay 503

2. Single cell gel electrophoresis 506

3. In vitro Chromosome aberration test 507

4. In vivo Micronucleus test 508

Section 4. Discussion 510

Section 5. Conclusions 513

Chapter 4. Achievements & Contributions 515

Chapter 5. Plans for practical use of results 516

Chapter 6. References 517

Appendix. Standard Operating Procedure(제목없음) 539

[Development of In vitro Phototoxicity Test etc.] 554

SUMMARY 560

Contents 565

Chapter 1. Introduction 574

Chapter 2. Current status of method development 582

Chapter 3. Contents and results of project and discussion 584

Section 1. Contents of project 584

Section 2. Results 594

Section 3. Discussion 611

Chapter 4. Achievements(Achivements) and Contributions 622

Chapter 5. Perspectives of the Applications of the Study 624

Chapter 6. References 625

Appendix 1. Standard operation procedure(SOP) 706

[Establishment(Estabilishment) of new Screening Methods for Anti-metastasis Drug using matrix Metalloproteinase (MMP) etc.] 717

SUMMARY 723

Contents 728

Chapter I. Introduction 729

Chapter III／II. Methods and results of the project 736

A. Methods 736

1. Determination of anti-metastatic assay in vitro 736

2. Determination of anti-metastatic activity of testing agents 738

3. In vivo anti-metastatic test 739

4. Identification of spontaneous metastasis related genes 739

5. Corelationship of metastasis and anti-tumor inhibitor by yakuchinone A and B 741

B. Results 743

1. In vitro anti-metastatic assay 743

2. In vitro assay of anti-metastatic agents 745

3. In vivo anti-metastatic test 746

4. Identification of spontaneous metastasis related genes 747

5. Anti-metastasis and anti-tumor effect of yakuchinone A and B 748

*Tables and Figures(제목없음) 751

Chapter IV／III. Conclusions 800

Chapter VI／IV. References 802

[Development of Antimetastatic Inhibitors from Health Food etc.] 806

SUMMARY 811

Contents 812

1. Introduction 815

2. Materials and Methods 822

1) Flow diagram of research 822

2) Selection of samples 822

3) Preparation of extracts from resource plants 825

4) Cells and incubation conditions 825

5) Assessment of inhibitory concentration(IC50) by MTT assay 825

6) Effect of extracts on MMP9P-SEAP expression 828

7) Gel zymography 829

3. Results 830

1) Selection of samples 830

2) Preparation of extracts from resource plants 830

3) Assessment of inhibitory concentration(IC50) by MTT assay 830

4) Effect of extracts on MMP9P-SEAP expression 835

5) Gel zymography 835

4. Conclusions 847

5／6. References 849

[Studies on the Medium-term in vivo Bioassay etc.] 851

Summary 862

Contents 872

Chapter 1. Introduction 873

Chapter 2. Justifications of the project 878

Chapter 3. Contents of project and Results 881

Section 1. Materials(Meterials) and Methods 881

1. 1st year 881

2. 2nd year 885

3. 3rd year 888

Section 2. Results 891

1. 1st year 891

2. 2nd year 897

3. 3rd year 902

4. Figures 907

Section 3. Discussion 912

Chapter 4. Achievement of project and Assistance 920

Chapter 5. Proposals for application of results 921

Chapter 6. References 922

Table 1. Hepatotoxicity of NSAIDs on Rat Hepatocytes 160

Table 2. In vivo Hepatotoxicity of NSAIDs 161

Table 1. Test material of surfactants 226

Table 2. Comparison of the cytotoxicity of surfactants exposed for 3 hrs by the NRU(neutral red uptake) and Alamar Blue method on human fibroblast cells and their in vivo potentials for skin irritation. 251

Table 3. Comparison of the cytotoxicity of surfactants exposed for 3 hrs by the NRU(neutral red uptake) and Alamar Blue reduction method on HaCaT cells and their in vivo potentials for skin irritation(irritaiton). 252

Table 4. Comparison of the cytotoxicity of surfactants exposed for 3 hrs by the MTT and Alamar Blue reduction method on HaCaT cells and their in vivo potentials for skin irritation(irritaiton). 253

Table 5. Comparison of the cytotoxicity of cell lines exposed for 3 hrs to surfactants by Alamar Blue reduction method on human fibroblast and HaCaT cells. 254

Table 6. Comparison of the cytotoxicity of humectants exposed for 72 hrs by the MTT, NRU(neutral red uptake) and Alamar Blue reduction method on human fibroblast cells and their in vivo potentials for skin irritation(irritaiton). 255

Table 7. Comparison of the cytotoxicity of humectants exposed for 72 hrs by the MTT, Alamar Blue and NRU(neutral red uptake) reduction method on HaCaT cells and their in vivo potentials for skin irritation(irritaiton). 256

Table 8. In vitro cytotoxicity of surfactants exposed for 3 hrs by the MTT reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 257

Table 9. In vitro cytotoxicity of surfactants exposed for 3 hrs by the Alamar Blue reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 258

Table 10. In vitro cytotoxicity of surfactants exposed for 3 hrs by the NRU(neutral red uptake) reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 259

Table 11. In vitro cytotoxicity of humectants exposed for 72 hrs by the MTT reduction method on human fibroblast cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 260

Table 12. In vitro cytotoxicity of humectants exposed for 72 hrs by the Alamar Blue reduction method on human fibroblast cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 261

Table 13. In vitro cytotoxicity of humectants exposed for 72 hrs by the NRU(neutral red uptake) reduction method on human fibroblast cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 262

Table 14. In vitro cytotoxicity of humectants exposed for 3 hrs by the MTT reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 263

Table 15. In vitro cytotoxicity of humectants surfactants exposed for 72 hrs by the Alamar Blue reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 264

Table 16. In vitro cytotoxicity of humectants surfactants exposed for 72 hrs by the NRU reduction method on human keratinocyte (HaCaT) cells listed in order of IC10, IC20, IC50 and IC80 values(㎍／ml).(이미지참조) 265

Table 17. Correlation of surfactants between in vivo and in vitro methods in human fibroblast cells on the basis of their IC50(이미지참조) values. 266

Table 18. Correlation of surfactants between and in vitro methods in human keratinocyte cells on the basis of their IC50(이미지참조) values. 266

Table 19. Correlation of surfactants between in vivo and in vitro methods in human fibroblast and keratinocyte cells on the basis of their IC50(이미지참조) values. 267

Table 1. Gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells with mutagens 521

Table 2. Gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells with isophorone reported unique positive chemical for MAL assay 522

Table 3. Gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells with ellagic acid 523

Table 4. Gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells with the methanol extract of Ecklonia stolonifera 524

Table 5. Inhibitory effects of ellagic acid on isophorone induced genotoxicity using gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells 525

Table 6. Inhibitory effects of the methanol extract of Ecklonia stolonifera on cyclophosphomide induced genotoxicity using gene mutation assay in mouse lymphoma tk+／-(이미지참조) L5178Y cells 526

Table 7. Chromosome(Chrmosome) aberration test of methyl methanesulfonate during 24 hours in CHL cells without metabolic activation 527

Table 8. Inhibitory effects of ellagic acid on MMC induced chromosome(chrmosome) aberrations in CHL cell without metabolic activation 528

Table 9. Inhibitory effects of ellagic acid on B(a)P induced chromosome(chrmosome) aberration in CHL cell with metabolic activation 529

Table 10. Preliminary tests of inhibitory of ellagic acid on the MMC(2mg／kg／10㎖) induced MNPCEs by different treatment times of ellagic acid in ddY male mice 530

Table 11. Inhibitory effects of ellagic acid on the MMC induced MNPCEs in ddY male mice 531

Table 12. Inhibitory effects of E. stolonifera on the MMC induced MNPCEs in ddY male mice 532

Table 13. Inhibitory effects of E. stolonifera on the MMC induced MNPCEs in ddY male mice 533

Table 1. Phototoxicity and cytotoxicity of different concentrations of doxycycline using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 631

Table 2. Phototoxicity and cytotoxicity of different concentrations of oxytetracycline using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 632

Table 3. Phototoxicity and cytotoxicity of different concentrations of tetracycline using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 633

Table 4. Phototoxicity and cytotoxicity of different concentrations of ketoprofen using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 634

Table 5. Phototoxicity and cytotoxicity of different concentrations of naproxen using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 635

Table 6. Phototoxicity and cytotoxicity of different concentrations of sulindac using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 636

Table 7. Phototoxicity and cytotoxicity of different concentrations of griseofulvin using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 637

Table 8. Phototoxicity and cytotoxicity of different concentrations of anthracene using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 638

Table 9. Phototoxicity and cytotoxicity of different concentrations of sodium lauryl sulfate using MTT, neutral red uptake and MTS assays in human fibroblast cultures. 639

Table 10. In vitro phototoxicity of several chemicals using MTT assay in human fibroblast cultures. 640

Table 11. In vitro phototoxicity of several chemicals using neutral red uptake assay in human fibroblast cultures. 641

Table 12. In vitro phototoxicity of several chemicals using MTS assay in human fibroblast cultures. 642

Table 13. Phototoxic effects of several chemicals depend on concentration of chemicals and UVA dose in Candida albicans. 643

Table 14a. Phototoxicity responses of ketoprofen, naproxen and sulindac in guinea pig. 644

Table 14b. Phototoxicity responses of oxytetracycline, doxycycline, tetracycline in guinea pig. 645

Table 14c. Phototoxicity responses of griseofulvin, anthracen, sodium lauryl sulfate in guinea pig. 646

Table 15a. Histological changes in the skin of guinea pig 48 hour after various drug treatment. 647

Table 15b. Histological changes in the skin of guinea pig 48 hour after various drug treatment. 648

Figure 1. Chemical structures of the 6 NSAIDs studied. 162

Figure 2. Dose-response curves for LDH release from primarily-cultured rat hepatocytes exposed for 18hr to the NSAIDs. Each value represents the mean±standard error (n＝6) 163

Figure 3. Dose-response curves for GPT release from primarily-cultured rat hepatocytes exposed for 18hr to the NSAIDs. Each value represents the mean±standard error (n＝6) 164

Figure 4. In vitro hepatotoxicity of NSAIDs using the LDH, GPT, SDH assays.... 165

Figure 5. In vitro-in vivo correlations of LDH, GPT, SDH activities 166

Figure 6. Effects of aluminum chloride on the growth of reaggregated cells derived from 2 day old Long-Evans rat cerebellum.... 167

Figure 7. Effects of superoxide dismutase on the growth of reaggregated cells derived from 2 day old Long-Evans rat cerebellum.... 168

Figure 8. Effects of superoxide dismutase on the growth of reaggregated cells derived from 2 day old Long-Evans rat cerebellum treated with aluminum chloride.... 169

Figure 9. Effects of NMDA and L-glutamate on cyclic GMP response in 8 day old Long-Evans rat slices.... 170

Figure 10. Phase-contrast micrograph of proximal tubular cell isolated from rat kidney on the fifth day(A) and on the ninth day(B) after seeding.... 171

Figure 11. Effect of cisplatin on α-MG uptake The cells were incubated with various concentrations of cisplatin for 5 hrs.... 172

Figure 12. Effect of cisplatin on α-MG uptake The cells were incubated with various concentrations of cisplatin for 24 hrs.... 173

Figure 13. Effect of cisplatin on intracellular ATP content The cells were incubated with various concentrations of cisplatin for 5 or 24 hrs.... 174

Figure 14. Effect of cisplatin on viability as assessed by MTT assay The cells were incubated with various concentrations of cisplatin for 5 or 24 hrs.... 175

Figure 15. Effect of cisplatin on activity of NA+-K+(이미지참조) ATPase The cells were incubated with various concentrations of cisplatin for 5 or 24 hrs.... 176

Figure 16. Effect of cisplatin on ALP activity The cells were incubated with various concentrations of cisplatin for 5 or 24 hrs.... 177

Figure 17. Schematic representation of a proximal tubular cell indicating functional relationship between intracellular ATP concentration and α-MG uptake.... 178

Figure 1. Correlation between NRU(neutral red uptake) reduction scores of surfactants in fibroblast cell and human patch test irritancy rank. 268

Figure 2. Correlation between NRU reduction scores of surfactants in fibroblast cells and rabbit intradermal safety test rank. 269

Figure 3. Correlation between Alamar Blue reduction scores(by IC50(이미지참조)) of surfactants in fibroblast cell and human patch test irritancy rank. 270

Figure 4. Correlation between Alamar Blue reduction scores(by IC50(이미지참조)) of surfactants in fibroblast cell and rabbit intradermal safety test rank. 271

Figure 5. Correlation between Alamar Blue reduction scores(by IC10(이미지참조)) of surfactants in fibroblast cell and human patch test irritancy rank. 272

Figure 6. Correlation between Alamar Blue reduction scores(by IC10(이미지참조)) of surfactants in fibroblast cell and rabbit intradermal safety test rank. 273

Figure 7. Correlation between MTT reduction scores(by IC50(이미지참조)) of surfactants in HaCaT cell and human patch test irritancy rank. 274

Figure 8. Correlation between MTT reduction scores(by IC50(이미지참조)) of surfactants in HaCaT cell and rabbit intradermal safety test rank. 275

Figure 9. Correlation between NRU reduction scores(by IC50(이미지참조)) of surfactants in HaCaT cell and human patch test irritancy rank. 276

Figure 10. Correlation between NRU reduction scores(by IC10(이미지참조)) of surfactants in HaCaT cell and human patch test irritancy rank. 277

Figure 11. Correlation between Alamar Blue reduction scores(by IC50(이미지참조)) of surfactants in HaCaT cell and human patch-test irritancy rank. 278

Figure 12. Correlation between Alamar Blue reduction scores(by IC50(이미지참조)) of surfactants in HaCaT cell and rabbit intradermal safety test rank. 279

Figure 13. Correlation between Alamar Blue reduction scores(by IC10(이미지참조)) of surfactants in HaCaT cell and human patch test irritancy rank. 280

Figure 14. Correlation between Alamar Blue reduction scores(by IC10(이미지참조)) of surfactants in HaCaT cell and rabbit intradermal safety test rank 281

Figure 15. Correlation between MTT reduction scores(by IC50(이미지참조)) of humectants in fibroblast cell and human patch test irritancy rank. 282

Figure 16. Correlation between MTT reduction scores(by IC50(이미지참조)) of humectants in HaCaT cell and human patch test irritancy rank. 283

Figure 17. Correlation between MTT reduction scores(by IC80(이미지참조)) of humectants in fibroblast cell and human patch test irritancy rank. 284

Figure 18. Correlation between Alamar Blue reduction scores(by IC50(이미지참조)) of humectants in fibroblast cell and human patch test irritancy rank. 285

Figure 19. Correlation between Alamar Blue reduction scores(by IC80(이미지참조)) of humectants in fibroblast cell and human patch test irritancy rank. 286

Figure 20. Correlation between Alamar Blue reduction scores(score) (by IC50(이미지참조)) of humectants in HaCaT cell and human patch test irritancy rank. 287

Figure 21. Correlation between NRU reduction scores(by IC50(이미지참조)) of humectants in fibroblast cell and human patch test irritancy rank. 288

Figure 22. Correlation between NRU reduction scores(by IC50(이미지참조)) of humectants in HaCaT cell and human patch test irritancy rank. 289

Fig. 1. Photographs of DNA migration patterns of CHL cells treated with different concentrations of H₂O₂ for 2 hours (A, untreated; B, 5×10-6M; C, 2.5×10-5M; D, 5×10-5M)(이미지참조) 534

Fig. 2. Frequency distributions of DNA migration of 50 representative(representiatve) nuclei from CHL cells treated with different concentrations of H₂O₂ for 2 hours 535

Fig. 3. Frequency distributions of DNA migration of 50 representative nuclei from Vero cell treated with different concentrations of H₂O₂ for 2 hours 536

Fig. 4. Frequency distributions of DNA migration of 50 representative nuclei from CHL cells treated with different concentrations of MMS for 2 hours 537

Fig. 5. Frequency distributions of DNA migration of 50 representative nuclei from Vero cells treated with different concentrations of MMS for 2 hours 538

Figure 1. Absorption spectra of doxycycline 649

Figure 2. Absorption spectra of oxytetracycline 649

Figure 3. Absorption spectra of tetracycline 650

Figure 4. Absorption spectra of ketoprofen 650

Figure 5. Absorption spectra of naproxen 651

Figure 6. Absorption spectra of sulindac 651

Figure 7. Absorption spectra of griseofulvin 652

Figure 8. Absorption spectra of anthracene 652

Figure 9. Absorption spectrum of sodium lauryl sulfate 653

Figure 10. Absorption spectrum of sodium lauryl sulfate after UV irradiation 653

Figure 11. IR spectra of doxycycline 654

Figure 12. IR spectra of oxytetracycline 654

Figure 13. IR spectra of tetracycline 655

Figure 14. IR spectra of ketoprofen 655

Figure 15. IR spectra of naproxen 656

Figure 16. IR spectra of sulindac 656

Figure 17. IR spectra of griseofulvin 657

Figure 18. IR spectra of anthracene 657

Figure 19. IR spectra of sodium lauryl sulfate 658

Figure 20. ¹H-NMR spectrum of doxycycline 659

Figure 21. ¹H-NMR spectrum of doxycycline after irradiation 659

Figure 22. ¹H-NMR spectrum of oxytetracycline 660

Figure 23. ¹H-NMR spectrum of oxytetracycline after irradiation 660

Figure 24. ¹H-NMR spectrum of tetracycline 661

Figure 25. ¹H-NMR spectrum of tetracycline after irradiation 661

Figure 26. ¹H-NMR spectrum of ketoprofen 662

Figure 27. ¹H-NMR spectrum of ketoprofen after irradiation 662

Figure 28. ¹H-NMR spectrum of naproxen 663

Figure 29. ¹H-NMR spectrum of naproxen after irradiation 663

Figure 30. ¹H-NMR spectrum of sulindac 664

Figure 31. ¹H-NMR spectrum of sulindac after irradiation 664

Figure 32. ¹H-NMR spectrum of griseofulvin 665

Figure 33／32. ¹H-NMR spectrum of griseofulvin after irradiation 665

Figure 34／33. ¹H-NMR spectrum of anthracen 666

Figure 35／34. ¹H-NMR spectrum of anthracen after irradiation 666

Figure 36. ¹H-NMR spectrum of sodium lauryl sulfate 667

Figure 37. ¹H-NMR spectrum of sodium lauryl sulfate after irradiation 667

Figure 38. Concentration - response curve for the phototoxicity and cytotoxicity of doxycycline determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝5). 668

Figure 39. Concentration - response curve for the phototoxicity and cytotoxicity of oxytetracycline determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~6). 669

Figure 40. Concentration - response curve for the phototoxicity and cytotoxicity of tetracycline determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~8). 670

Figure 41. Concentration - response curve for the phototoxicity and cytotoxicity of ketoprofen determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 671

Figure 42. Concentration - response curve for the phototoxicity and cytotoxicity of naproxen determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝7~8). 672

Figure 43. Concentration - response curve for the phototoxicity and cytotoxicity of sulindac determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 673

Figure 44. Concentration - response curve for the phototoxicity and cytotoxicity of griseofulvin determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~5). 674

Figure 45. Concentration - response curve for the phototoxicity and cytotoxicity of anthracene determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 675

Figure 46. Concentration - response curve for the phototoxicity and cytotoxicity of sodium lauryl sulfate determined by MTT assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 676

Figure 47. Concentration - response curve for the phototoxicity and cytotoxicity of doxycycline determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝5). 677

Figure 48. Concentration - response curve for the phototoxicity and cytotoxicity of oxytetracycline determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~6). 678

Figure 49. Concentration - response curve for the phototoxicity and cytotoxicity of tetracycline determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~8). 679

Figure 50. Concentration - response curve for the phototoxicity and cytotoxicity of ketoprofen determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 680

Figure 51. Concentration - response curve for the phototoxicity and cytotoxicity of naproxen determined by NR uptake using human fibroblast cells. Each point represents the mean±S.E.(n＝7~8). 681

Figure 52. Concentration - response curve for the phototoxicity and cytotoxicity of sulindac determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 682

Figure 53. Concentration - response curve for the phototoxicity and cytotoxicity of griseofulvin determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~5). 683

Figure 54. Concentration - response curve for the phototoxicity and cytotoxicity of anthracene determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 684

Figure 55. Concentration - response curve for the phototoxicity and cytotoxicity of sodium lauryl sulfate determined by NR uptake assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 685

Figure 56. Concentration - response curve for the phototoxicity and cytotoxicity of doxycycline determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝5). 686

Figure 57. Concentration - response curve for the phototoxicity and cytotoxicity of oxytetracycline determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~6). 687

Figure 58. Concentration - response curve for the phototoxicity and cytotoxicity of tetracycline determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~8). 688

Figure 59. Concentration - response curve for the phototoxicity and cytotoxicity of ketoprofen determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 689

Figure 60. Concentration - response curve for the phototoxicity and cytotoxicity of naproxen determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝7~8). 690

Figure 61. Concentration - response curve for the phototoxicity and cytotoxicity of sulindac determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 691

Figure 62. Concentration - response curve for the phototoxicity and cytotoxicity of griseofulvin determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝4~5). 692

Figure 63. Concentration - response curve for the phototoxicity and cytotoxicity of anthracene determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 693

Figure 64. Concentration - response curve for the phototoxicity and cytotoxicity of sodium lauryl sulfate determined by MTS assay using human fibroblast cells. Each point represents the mean±S.E.(n＝8). 694

Figure 65. Dose - response curves of the yeast inhibition zones for Candida albicans at concentration of 0.1, 1, 10% doxycycline with UVA. Data shown are mean±S.D. of three separate experiments. 695

Figure 66. Dose - response curves of the yeast inhibition zones for Candida albicans at concentration of 0.1, 1, 10% ketoprofen with UVA. Data shown are mean±S.D. of three separate experiments. 696

Figure 67. Dose - response curves of the yeast inhibition zones for Candida albicans at concentration of 0.1, 1, 10% naproxen with UVA. Data shown are mean±S.D. of three separate experiments. 697

Figure 68. Dose - response curves of the yeast inhibition zones for Candida albicans at concentration of 0.1, 1, 10% sulindac with UVA. Data shown are mean±S.D. of three separate experiments. 698

Figure 69. Dose - response curves of the yeast inhibition zones for Candida albicans at concentration of 0.001, 0.01, 0.1% anthracene with UVA. Data shown are mean±S.D. of three separate experiments. 699

Figure 70. Phototoxic effect of ketoprofen. Photomicrograph of culture of human fibroblasts incubated with ketoprofen(upper) followed by UV exposure and normal human fibroblasts(lower). 700

Figure 71. Phototoxic effect of ketoprofen(A) and naproxen(B) in Candida albicans plates. The plate on the left shows phototoxic responses. Non-irradiated control is on the right. 701

Figure 72. Phototoxic effect of doxycycline(A) and anthracene(B) in Candida albicans plates. The plate on the left shows phototoxic responses. Non-irradiated control is on the right. 702

Figure 73. Phototoxicity test of ketoprofen(A) and naproxen(B) in guinea pig. 703

Figure 74. Upper panel : Photomicrograph of ketoprofen-applied skin irradiated with UV to elict phototoxicity 48 hours after cessation of the treatment. Lower panel : Photomicrograph of control skin 704

Figure 75. Upper panel: Photomicrograph of griseofulvin-applied skin irradiated with UV to elict phototoxicity 48 hours after cessation of the treatment.... 705