Prologue
Assessment of Human Cancer Risk: Challenges for Alternative Approaches
Background and Framework for ILSI's Collaborative Evaluation Program on Alternative Models for Carcinogenicity Assessment
Criteria for the Evaluation of Studies in Transgenic Models
The Nature of the Heterozygous Trp 53 Knockout Model for Identification of Mutagenic Carcinogens
p53+/− Hemizygous Knockout Mouse: Overview of Available Data
The Tg.AC (v-Ha-ras) Transgenic Mouse: Nature of the Model
Tg.AC Genetically Altered Mouse: Assay Working Group Overview of Available Data
The rasH2 Transgenic Mouse: Nature of the Model and Mechanistic Studies on Tumorigenesis
CB6F1-rasH2 Mouse: Overview of Available Data
DNA Repair-Deficient Xpa and Xpa/p53 +/− Knock-Out Mice: Nature of the Models
Xpa and Xpa/p53 +/− Knockout Mice: Overview of Available Data
Neonatal Mouse Model: Review of Methods and Results
The Syrian Hamster Embryo (SHE) Cell Transformation Assay: Review of the Methods and Results
Is p53 Haploinsufficient for Tumor Suppression? Implications for the p53+/− Mouse Model in Carcinogenicity Testing
Mechanisms of Hormonal Carcinogenesis in the p53+/− Hemizygous Knockout Mouse: Studies With Diethylstilbestrol
Comparison of the Levels of Enzymes Involved in Drug Metabolism between Transgenic or Gene-knockout and the Parental Mice
A Perspective on Current and Future Uses of Alternative Models for Carcinogenicity Testing
Expectations for Transgenic Rodent Cancer Bioassay Models
Alternative Models for Carcinogenicity Testing: Weight of Evidence Evaluations Across Models
Panel Discussion on the Application of Alternative Models to Cancer Risk Assessment
Epilogue
Overview
Neonatal Mouse Model for Short-Term Carcinogenicity Testing
Cyclophosphamide Results in the Neonatal Mouse Model
Induction of Drug Metabolism-Related Enzymes by Methylcholanthrene and Phenobarbital in Transgenic rasH2 Mice and Their Wild-Type Littermates
Testing of Clofibrate in a One-Year Neonatal CD-1 Mouse Assay
1-Year Tumorigenicity Study of 17β-Estradiol in Neonatal Mice
Results of a 12-Month Oral Carcinogenicity Study with Haloperidol in the Neonatal Swiss Mouse
The p53+/− Heterozygous Knockout Mouse Model for Short-Term Carcinogenicity Testing
Testing of Clofibrate in a 6-Month Gavage Study Using p53+/− Mice
26-Week Oncogenicity Study with DI(2-Ethylhexyl)Phthalate (DEHP) in p53 Heterozygous Mice
Carcinogenicity Assessment of Phenobarbital and Sulfamethoxazole in p53+/− Mice
26-Week Oral Gavage Carcinogenicity Study of 17β-Estradiol in Male and Female p53+/− Mice
Carcinogenic Responses of Heterozygous p53 Knockout Mice to Orally Administered Cyclophosphamide
Investigation into the Hepatic Effects of the Peroxisome Proliferator, WY-14,643, on p53+/− Mice After 6 Months Dietary Administration
Short-Term Bioassay on the Non-Carcinogen “Ampicillin” in p53 Hemizygous (+/−) Mice
Effect of 6-Month Dietary Administration of Methapyrilene Hydrochloride in p53 Knockout Mice
A 6-Month Oral Gavage Carcinogenicity Study in p53 +/− Transgenic Mice with the Antihistamine Methapyrilene Hydrochloride
26-Week Oral Gavage Carcinogenicity Study of Haloperidol in Male and Female p53+/− Mice
Evaluation of Water Disinfection By-Products Using p53def and Tg.AC Transgenic Mouse Models
Lack of Susceptibility of rasH2 Mice, Heterozygous p 53 -Knockout CBA Mice, and Heterozygous p 53 -Knockout CIEA Mice to Phenolphthalein in a 6-Month Carcinogenicity Study
Carcinogenicity and Co-Carcinogenicity of Sodium Arsenite in p53 +/− Male Mice
Chemical-Induced Tumorigenesis in the p 53 -Haploinsufficient Tg.AC (Hemizygous V-HA- RAS ) Mouse Model
Non-Genotoxic Carcinogenicity in p53+/− Mice After 26 Weeks of Subcutanous Dosing with Antioxidants
Testing of Clofibrate, Benzene, 12-0-Tetradecanoyl Phorbol 13 Acetate, Dimethylvinylchloride, p -Cresidine, and Cyclophosphamide in Micronucleus Assays in p53+/−, p53+/+, Tg.AC Hemizygous, and FVB Mice
Altered Expression of Genes Involved in Cell Cycle Control and Apoptosis in p53 +/+ and p53 +/− Mice Exposed to Benzene
Investigation into Gene Expression Profile Differences in Diethylstilbestrol (DES) Treated p53+/− and Wild-Type Mice
Providing Information for Regulatory Decisions: Phenolphthalein Studies in the p53(+/−) Mouse
Development of an In Vitro p53 Mutagenicity Assay
Mechanisms for Differential Loss of the Wild-Type Trp53 Allele in Tumors Induced in the Heterozygous p53 Deficient (+/−) Mouse
The p53 Haploinsufficient C57BL/6 (N5) Mouse Model and Identification of Mutagenic Chemical Carcinogens
Attenuated p53 Response to Genotoxic Stress in Preneoplastic Alterations in Rat and Mouse Liver
Spontaneous Tumor Profile in the p53 Deficient Tg.AC (v-Ha-ras) Bigenic Mouse Model
Genotoxicity, Recombination, and Tumor Development in C57BL/6- P53 +/− Mice Exposed to Inhaled Benzene
A Comparison of Toxicity and Tumorigenesis in two Strains of P53-Heterozygous Mice: The Response to Inhaled Bromodichloromethane
The Carcinogenic Response of Transgenic XPA-/- and XPA-/- P53+/- Mice to Oral Administration of Estradiol-17β
No Induction of Neoplasia or Proliferation in P53Hemizygous (+/−) Mice after Exposure to 4-(N-Methyl-N-Nitrosamino)-1-(3-Pyridyl)-1-Butanone (Liver, Lung) and Diethylnitrosamine (Liver)
CB6F1-T gras H2 Mice: Its Profile and Standard Design for a 26-Week Alternative Carcingenicity Study
26-Week Carcinogenicity Study of Ampicillin in CB6F1-Tg-rasH2 Mice
Effects of Clofibrate in the CB6F1-TG-RASH2 Mouse
26-Week Carcinogenicity Study of Chlorpromazine in CB6F1-Tg-rasH2 Mice by Dietary Dosing
Detection of Carcinogenic Potential of Diethylstilbestrol and N -Methyl- N -Nitrosourea by the Alternative Testing Model Using Tg-rasH2 Mouse
Testing of Clofibrate in A Six-Month Gavage Study Using Rash2 Mice
Utility of Transgenic Mice Carrying Human Prototype C-Ha- Ras Gene for Alternative Carcinogenicity Testing of Chemicals-Negative Results with Methapyrilene Hydrochloride
26-Week Carcinogenicity Study of Chloroform in CB6F1-RASH2 Transgenic Mice
26-Week Carcinogenicity Study of Metoproterenol Sulfate in Tg-rasH2 Mice
26-Week Carcinogenicity Study of Sulfamethoxazole in CB6F1-Tg-rasH2 Mice
DI(2-Ethylhexyl) Phthalate Induces Hepatocellular Neoplasm in Male rasH2 MICE in 26-Week Carcinogenicity Study
Results of a 6-Month Oral Carcinogenicity Study with 17-β-estradiol in Transgenic TgHras2 and Wild-Type cb6fl Mice
Results of a 6-Month Oral Carcinogenicity Study with Haloperidol in Transgenic TgHras2 and Wild-Type CB6F1 Mice
Lack of Susceptibility of rasH2 Mice, Heterozygous p53-Knockout CBA Mice, and Heterozygous p53-Knockout CIEA Mice to Phenolphthalein in a 6-month Carcinogenicity Study
26-Week Carcinogenicity Study of Phenobarbital in CB6F1-Tg rasH2 Mice and Examination of Hepatic Carcinogenicity of Phenobarbital in CB6F1-Tg rasH2 Mice Initiated with N-Diethylnitrosamine
Tumor Development in CB6Fl-Tg-rasH2 Mice Given Cyclophosphamide Once Weekly for 26 Weeks
Effect of Intestinal Bacteria and Functional Foods on Incidence of Colorectal Tumors Induced by 1,2-Dimethylhydrazine (DMH) Injection in Transgenic (TG) Mice Harboring Human Prototype C-HA-RAS Genes
Overexpression of Human H-ras Transgene in Tumors of rasH2 Mice Induced by Ethyl- and Methyl-Nitrosourea
Rapid Carcinogenicity Testing of 1,4-Dioxane, Ethylene Thiourea, Cholestyramine, and Sulfisoxazole Using Tg-rasH2 Mice
Assessment of Transgene Orientation in the Tg-rasH2 Transgenic Mouse: A Critical Step in Monitoring Transgene Stability of Microinjected Animals
Molecular Biological Studies in the rasH2 Transgenic Mouse
Sequential Histopathological Study on Tg-rasH2 Mice After Administration of MNU
The XPA−/− and XPA−/− .p53+/− Knockout Mouse Models for Short-Term Carcinogenicity Testing
39-Week Oral Carcinogenicity Study with Cyclosporin A in XPA−/− Mice, Wild Type Mice, and XPA−/−, P53+/− Double Transgenic Mice
The Carcinogenic Response of Transgenic XPA−/− and XPA−/− P53+/− Mice to Oral Administration of Estradiol-17β
Carcinogenicity Testing of Ampicillin in the XPA−/− Mouse
Wy-14,643: 4-Week Dietary Dose Range Finding Study and 39-Week Carcinogenicity Study in XPA−/− Mice
Short-Term (9-Month) Carcinogenicity Study with Haloperidol in Transgenic XPA−/− and Double Transgenic XPA−/− .p53+/− Mice
9-Month Oral Toxicity Study with Sulfamethoxazole in XPA−/−, XPA−/− /p53+/−, and C57B1/6 Mice
Diethylstilbestrol (DES): An Assessment of Carcinogenicity in XPA−/−, XPA−/−p53+/−, and Wild-Type Mice Following 9 Months Dietary Exposure
Di(2-Ethylhexyl)Phtalate (DEHP): An Assessment of Carcinogenicity in XPA−/−, Wild-Type, and XPA−/− p53+/− Mice Following 39 Weeks' Dietary Exposure
Results of 9-Month Carcinogenicity Testing with Phenobarbital in Transgenic XPA−/− and XPA−/− .P53+/− Mice and Wild-Type C57BL/6 Mice
Concurrent Positive Control Studies with p-Cresidine and 2-AAF in Wild-Type, XPA−/−, and XPA−/−, p53+/− Mice
The Effect of Heterozygous Loss of P53 on Chemically Induced Mutations and Tumors in DNA Repair-Deficient XPA Mice
Characteristics of the Tg.AC Transgenic Mouse Model
26-Week Dermal and Oral Gavage Dose Range-Finding and Carcinogenicity Bioassay in Tg.AC Hemizygous (FVB/N) Mice
Evaluation of Water Disinfection By-Products Using p53def and Tg.AC Transgenic Mouse Models
Analysis of Responder Status Across Multiple Generations of Tg.AC Transgenic Mice
The Nonresponder Phenotype in Tg.AC Mice is Produced by Loss of Palindromic Symmetry in Transgene Promoter Sequence
Quality Control of Foundation and Production Colonies and Spontaneous Nonresponder Frequency of TG.AC Transgenic Mice
A 6-Month Dermal (Skin Painting) Carcinogenicity Study in Tg.AC Transgenic Mice With the Antihistamine Methapyrilene Hydrochloride
Testing of Clofibrate in a 6-Month Dermal Administration Study Using Tg.AC Hemizygous Mice
Chemical-Induced Tumorigenesis in the p53 -Haploinsufficient Tg.AC (Hemizygous V-HA- RAS ) Mouse Model
Carcinogenic Endpoint Evaluation in Tg.AC Transgenic Mice Given Cyclosporin A Dermally for 26 Weeks
Comparative Route Studies in Tg.AC Homozygous Mice
26-Week Oral Toxicity Study with Sulfamethoxazole in Tg.AC Mice
Optimization of the Tg.AC Transgenic Mouse Model: I. Assessment of the Effects of Dermal and Oral Administration of Sulfisoxazole in Male and Female Hemizygous Mice
Optimization of the Tg.AC Transgenic Mouse Model: II. Assessment of the Effects of Dermal and Oral Administration of Phenobarbital in Male and Female Hemizygous Mice
Optimization of the Tg.AC Transgenic Mouse Model: III. Effect of Vehicle on Responsiveness of Hemizygous Tg.AC Mice to Dermal Applications of Phorbol 12-Myristate 13-Acetate (TPA)
Testing of Clofibrate in a 6-Month Gavage Study Using Tg.AC Hemizygous Mice
Toxicity Associated with Topical Exposure of v-ha-ras Tg.Ac Mice to the Plant-Derived Insecticide Rotenone
Dose- and Time-Response Studies for Skin Tumors with 2,3,7,8-TCDD in Tg.AC Mice after Dermal and Oral Exposure
Testing of Clofibrate, Benzene, 12-0-Tetradecanoyl Phorbol 13 Acetate, Dimethylvinylchloride, p -Cresidine, and Cyclophosphamide in Micronucleus Assays in p53+/−, p53+/+, Tg.AC Hemizygous, and FVB Mice
Age-Related Changes in Skin Tumor Induction and Transgene Expression in v-Ha-Ras Transgenic Tg.AC Mice
Oral Administration of Dimethylvinyl Chloride in Tg.AC Mice Induces v-Ha-Ras Transgene Expression in Forestomach Papillomas
Molecular and Genetic Analyses of the Mutant Frequency of Non-Responder Tg.AC Mice
A Critical Assessment of Transgenic Mouse Assays for Carcinogenicity Testing
Correlation of a Genotype with a Phenotype to Quality Control and Stabilize the Responder Transgene in a Production Colony of Tg.AC Transgenic Mice
Radial Transformation-Associated Recombination Cloning from the Mouse Genome: Isolation of Tg.AC Transgene with Flanking DNAs
Molecular Characterization of the Tg.AC Transgene Zeta-Globin Promoter
Spontaneous Tumor Profile in the p53 Deficient Tg.AC (v-Ha-ras) Bigenic Mouse Model
Cyclosporin A: 6-Month Carcinogenicity Study in Transgenic Mice
Summary of 50 Chemical Agents Tested in the Tg.AC Transgenic Mouse Model
Evaluation of the Specificity of the Tg.AC Assay by Testing Three Noncarcinogenic Pharmaceuticals that Induce Selected Stress Gene Promoters In Vitro
The Syrian Hamster Embryo (SHE) Cell Transformation Assay: Review of the Methods Used in the ILSI/HESI Program on Alternative Carcinogenicity Testing
Update on the Syrian Hamster Embryo (SHE) Cell Transformation Assay: Results from the ILSI/HESI Program on Alternative Carcinogenecity Models, and Analysis of 96 Chemical Database
Some Recommendations from an ECVAM Workshop on Cell Transformation Assays as Predictors of Carcinogenicity
Evaluation of the Syrian Hamster Embryonic (SHE) Assay as Predictive Screening Tool in Carcinogenic Hazard Identification
Screening for Carcinogens Devoid of Mutagenic Activity Using Morphological Transformation and Gap Junction Intercellular Communication in Syrian Hamster Embryo Cells
Interpretation of the Response to Potential Renal Carcinogens in the TSC2 Spontaneous Knockout (EKER) Rat is Dependent on Length of Treatment
The K6/ODC Transgenic Mouse: A Sensitive Model for Carcinogen Detection
Summary of Test Results of Medium-Term Carcinogenesis Bioassays Targeting the Liver or Multi-Organs
Ampicillin Trihydrate
Chloroform
Chlorpromazine Hydrochloride
Clofibrate
Cyclophosphamide
Cyclosporin A
Di(2-ethylhexyl) Phthalate
Dieldrin
Diethylstilbestrol
D-Mannitol
17-β-Estradiol
Haloperidol
Melphalan
Metaproterenol
Methapyrilene Hydrochloride
Phenacetin
Reserpine
Sodium Phenobarbital
Sulfamethoxazole
Sulfisoxazole
Wy-14,643
Appendix III: Published Reference Lists for Several Alternative Models for Carcinogenicity Testing