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Title
DECLARATION
CERTIFICATE
Aknowledgement
CONTENTS
1 Introduction & Review of Literature
INTRODUCTION
REVIEW OF LITERATURE
1.CANCER AND FACTORS LEADING TO CANCER
1.1 ROLE OF ENVIRONMENT
1.1.1 Chemical and physical carcinogens.
1.1.2 Estrogens and other hormones.
1.1.3. Roentgen and ultraviolet radiations.
1.1.4. Oncogenic Viruses.
1.1.5. Parasites.
1.1.6. Role of heredity.
1.2 THE PROCESS OF CARCINOGENESIS
1.3. REACTIVE OXYGEN SPECIES
1.3.1. Reactions of free radicals in biological systems.
1.3.2. Free radicals and DNA strand breaks.
1.3.3. Mutations and Chromosome changes.
1.3.4. Activation of xenobiotic carcinogens.
1.3.5. Tumour promotion and free radicals.
1.3.6. Inflammatory Responses and Reactive Oxygen Species.
1.3.6.1. Cycloxygenase Products.
1.3.6.2 Lipoxygenase products
1.3.6.3 Antiinflammatory agents.
1.3.7 Other clinical conditions related to reactive oxygen species.
1.4 ANTIOXIDANTS
1.5 CANCER CHEMOPREVENTION.
1.5.1.1. Blocking agents
1.5.2. Suppressing agents
1.5.3 Chemopreventive agents of plant origin
1.6 BIOLOGICAL ACTIVITIES OF TURMERIC AND CURCUMIN.
1.6.1 Turmeric
1.6.2. Curcumin
2 Materials & Methods
2.1. TEST COMPOUNDS
2.1.1 Curcuminoids
2.1.2 Chalcones
2.2 CHEMICALS
2.3. INSTRUMENTS
2.4 CELL LINES
2.5. ANIMALS
2.6. IN VITRO CYTOTOXICITY STUDIES
2.6.1 Short term -in -vitro cytotoxicity assay.
2.6.2. Determination of cytotoxicity by tissue culture.
2.7. LIPOSOME ENCAPSULATION
2.8. DETERMINATION OF TUMOUR REDUCING ACTIVITY
2.8.1. Ascites tumour model
2.8.2 Solid tumour model
2.9 ANTIOXIDANT STUDIES
2.9.1. Superoxide scavenging activity
2.9.2 Lipid peroxidation inhibiting activity
2.9.3 Hydroxyl radical scavenging activity.
2.9.4 Inhibition of superoxide generation in vivo.
2.10. ANTIMUTAGENICITY ASSAY-AMES TEST
2.10.1 Preparation of S9 fraction.
2.10.2 Preparation of minimal agar plates.
2.10.3 Spizizens salt solution (10X)
2.10.4 Histidine / biotin solution (0.5mH)
2.10.5 Ames assay procedure
2.11 ANTICARCINOGENICITY TESTING
2.12 ANTIINFLAMMATORY STUDIES
2.13. ANTI BACTERIAL STUDIES
2.14 STATISTICAL ANALYSIS
3 Cytotoxic, tumour reducing and antioxidant studies of curcuminoids
3.1 INTORODUCTION
3.2. MATERIALS AND METHODS
3.2.1. Short term -in vitro cytotoxicity of curcuminoids
3.2.2. Cytotoxicity of the curcuminoids in tissue culture.
3.2.3. Liposome encapasulation of curcuminoids
3.2.4. Effect of curcuminoids on ascites tumour development.
3.2.5. Effect of curcuminoids-on solid tumour development.
3.2.6. Effect of curcuminoids on the inhibition of lipid peroxidation.
3.2.7. Effect of curcuminoids on the inhibitions of superoxide production.
3.2.8. Effect of curcuminoids on the inhibition of hydroxyl radical production.
3.2.9. Effect of curcuminoids on the inhibition of superoxide generation by macrophages activated with PMA.
3.3 RESULTS
3.3.1. In vitro cytotoxic activity of curcuminoids.
3.3.2. Cytotoxicity of the curcuminoids in tissue culture.
3.3.3. Effect of curcuminoids on ascites tumour development
3.3.4. Effect of curcuminoids on solid tumour development.
3.3.5. Effect of curcuminoids on the inhibition of lipid peroxidation.
3.3.6. Effect of curcuminoids on the inhibition of super oxide production.
3.3.7. Effect of curcuminoids on the inhibition of hydroxyl radical production.
3.3.8. Effect of curcuminoids on the inhibition of superoxide production -in -vivo.
3.4. DISCUSSION
4 Cytotoxic, tumour reducing and antioxidant studies of chalcones and related compounds
4.1. INTRODUCTION
4.2. MATERIALS AND METHODS
4.2.1 Cytotoxicity of chalcones & vitro.
4.2.2 Cytotoxicity of chalcones in tissue culture
4.2.3 Liposome encapsulation of chalcones.
4.2.4 Determination of tumour reducing activity
4.2.5. Determination of lipid peroxidation inhibiting activity.
4.2.6. Determination of Superoxide scavenging activity
4.2.7. Determination of hydroxyl radical scavenging activity.
4.2.8. Inhibition of Superoxide generation by macrophages activated with PMA
4.3. RESULTS.
4.3.1. Cytotoxicity of chalcones, & vitro.
4.3.2. Cytotoxicity of chalcones in tissue culture
4.3.3. Tumour reducing activity of the chalcones
4.3.4. Effect of chalcones on the inhibition of lipid peroxidation.
4.3.5. Effect of chalcones on the inhibition of superoxide production
4.3.6. Effect of chalcones on the inhibition of hydroxyl radical production.
4.3.7. Effect of chalcones on the inhibition of PMA induced superoxide production.
4.4. DISCUSSION
5 Antimutagenic and anticarcinogenic studies of curcuminoids
5.1 INTRODUCTION
5.2 MATERIALS AND METHODS
5.3. PREPARATION OF S9 FRACTION.
5.4 ANTIMUTAGENICITY ASSAY
5.5 ANTICARCINOGENICITY TESTING
5.6 RESULTS
5.6.1 Antimutagenic Activity of Curcuminoids
Fig. 5.1 Papilloma formation on mouse treated with DMBA and croton oil.
5.6.2 Anticarcinogenic activity of the curcuminoids.
DISCUSSION
6 Anti-inflammatory and antibacterial studies of curcuminoids and chalcones
6.1 INTRODUCTION
6.2 MATERIALS AND METHODS.
6.2.1 Determination of Antiinflammatory activity.
6.2.2 Determination of antibacterial activity.
6.3 RESULTS
6.3.1 Antiinflammatory activity of natural curcuminoids.
6.3.2. Antiinflammatory activity of synthetic curcuminoids.
6.3.3. Antiinflammatory activity of sydnone substituted chalcones.
6.3.4. Antibacterial activity of natural curcuminoids
6.3.5. Antibacterial activity of synthetic curcuminoids.
6.3.6. Effect of light on antibacterial activity of the curcuminoids.
6.4 DISCUSSION
7 Summary and Conclusion
APPENDIX
BIBILIOGRAPHY
List of Publications