Biochemistry of cancer By Dr, Subodhini Abhang For Ist MBBS students. 1 To 28 gives an over view of cancer biochemistry

1. Dr. Subodhini Abhang

2.  Cell that is transformed .
Recognized by population of abnormal cells within the
normal tissue causing destruction of normal cell
population & behave like parasite.

3. A simplified hypothesis for development of cancer
Inactive anti-oncogenes Diminish
regulation by
apoptosis gene
Oncogenic Mutations
viruses
Environmental
factors( physical and
chemical)
Oncogene Activation
Carcinogenesis

4. Characteristics of differentiated cell
 Lack contact inhibition .
 Trap for nitrogen compounds.
 Site of growth.
 Loss of control on cell division.
 Decreased protein degradation as compared to synthesis.
 Transfer modified characters to daughter cells & subsequent
progeny.
 Loss of anchorage.

5. Causes of cancer
• Physical
• Chemical
• Biological

6. Effects of radiation
UV Rays X Rays Gama Rays
Mutagenic & Carcinogenic
Damage to DNA.
Pyrimidine dimers to form
Formation of apurinic or apyrimidinic sites.
Single & double strand break & cross linking
Free radical formation.( OH ͘ , super oxide)

7. Effects of radiation
Pyrimidine dimers

8. Chemical carcinogens
• 80% of cancer caused by chemicals
• Organic eg. benzo pyrine,
• Organic eg. benzo pyrine,
• chemicals
dimethylnitrosamine
Inorganic eg. Cadmium , Arsenic

9. How carcinogens enter in the body ?
Occupation ==== Asbestos, benzene
Diet --------------- Aflatoxin produced by fungus
(Aspergillus flavous) contamination with peanuts.
Drugs-------------- Diethylstilbestrol
Life style-----------Cigarette smoking
Two types ---- Direct
 Procarcinogens

10. Role of initiator & promoter
Initiator
Carcinogen
benzopyrene
Promotor
Croton oil
Potential tumor cells
Proliferating
cancer cells
Release & migration of cancer cells

11. Promotors
Promotor
• Cyclomates
• saccharin
• Metabolites of Tyrosine :
Phenol & cresol
Tryptophan: Indol & Indol
acetate
Tissue
• Tumor of Bladder
• Tumor of Gastrointestinal
tract.

12. Mechanism of action of chemical carcinogen
Pro -carcinogen proximate carcinogen
ultimate carcinogen
(highly reactive)
Electrophiles (deficient in
electrons)
Enzyme responsible for activation-----Cytochrome P450

13. Some chemical carcinogens
Class
• Polycyclic aromatic
hydrocarbons.
• Azo dyes (Aromatic amines)
• Nitrosamines
• Various drugs ( alkylating &
acetylating agents)
• Aflatoxins(fungus Aspergillus
Flavus)
Compound
• Benzo pyrene present in
cigarette smoke.
• An aniline azo dye Used in rubber
industry: ca.bladder.
• Synthesized in gut from ingested
nitrites or derived from digested
proteins: gastric cancer
• Stilbesterol.
• Mold.-- potent hepatic
carcinogen.

14. Oncogenes
Genes of viral origin which causes transformation of
target cell.
Rous 1911 ------ got Nobel prize in 1966
Sarcoma virus
DNA
RNA –mostly of retroviruses

15. Oncogenes play a crucial role in carcinogenesis
Oncogenes of Rous sarcoma virus:
gag pol env src
gag: Codes for group specific antigen
Pol: Reverse transcriptase
Env: certain glycoprotein of viral envelop
Src: protein tyrosine kinase

16. Mechanism of infective retrovirus formation
C DNA or
provirus
Retrovirus
Reverse transcriptase
Cell
Viral DNA
1.

17. Host DNA
Becomes a part of host DNA
1a.
Process of integration of viral genes into cellular DNA
Viral DNA

18. Mechanism by which proto-oncogene become oncogene
Proto-oncogene is the normal non mutated cellular
analog of oncogene.
1.
LTR
myc
myc
LTR
Provirus
Myc mRNA
e.g. Avian leukemia virus
Promotor insertion:

19. myc
myc
LTR LTR
provirus
2. Enhancer Insertion
Myc mRNA

20. 3. Translocation
Chromosome 4
Chromosome 4
Chromosome 20
Chromosome 20
Before After
In chronic granulocytic leukemia: Translocation between 9th and 22nd chromosome.

21. Break
Break
Gene for
H –Chains
myc gene
myc gene
Burkitt’s Lymphoma: chromosomal translocation
8 8 8
14 14 14
Heavy chains
Of immunoglobulin

22. 5. Gene amplification:
 Observed in many tumors.
 e.g . Methotrexate administration : leukemia
 Inhibitor of dihydrofolate reductase
 Dihydrofolate Tetra hydrofolate
- ---- required for sythesis of purines & thymine
 Tumor cells become resistant to this drug
Gene for dihydrofolate reductase becomes amplified
resulting in 400 fold increase in activity.

23. 5. Single point mutation
V-ras oncogene --------murine retrovirus
polypeptide related to G protein
modulates the activity
adenylate cyclase
role in cellular responses of hormones & drugs
C- ras oncogene -------DNA sequencing of C-ras protooncogene
Normal human bladder cells cancer of human bladder cells
Substitution of amino acid in 12 or 61 position results in GTPase
Chronic stimulation on adenylate cyclase

24. Mechanism of action of oncogenes:
1. Autocrine mechanism--- oncogene product is growth factor*
*
Over stimulation
2. Oncogene alters the receptor---- receptor is permanently turn on without
growth factor binding.
3. Transducer alteration:
Transduction –change in genetic make up of a cell
by transfer of viral DNA to cell.
Change in GTPase stimulatory protein Permanently turn on
results in uncoupling of normal
ligand receptor binding.

25. Tumor suppressor genes Or
Antioncogenes
 Protect an individual from getting cancer.
 Deletion removes the growth control of cells and
Believed to be a key factor in the development of tumor.
P⁵³ ----Absent in most tumors
RB gene ( retinoblastoma gene) located in chromosome 13
DCC gene--- Ca colon

26. Tumor markers.
The biochemical indicators employed to detect the presence of
cancer are collectively referred to as tumor markers.
- Abnormally produced molecules by tumor cells .
Eg. Surface antigens
cytoplasmic proteins
Enzymes
Hormones

27. Tumor markers.
Marker Associated cancer(s)
Oncofetal antigens
carcinoembryonic antigen(CEA)------------Colon, Stomach, Breast, Lung and Pancreas
alpha fetoprotein (AFP) ------------Liver and germ cells of testis
Cancer antigen ( CA 125) ------------Ovarian cancer of epithelial origin.
Prostate specific antigen ------------Prostate cancer
Hormons
Calcitonin ------------CA of medullary thyroid
Catecholamines and their
metabolites (VMA) -------------Neuroblastoma
Enzymes
Prosthetic acid phosphatase ------------ Prostate cancer
Neuron specific enolase ------------Neuroblastoma
Alkaline phosphatase(ALP) ------------Bone secondary's
Specific Proteins
Immunoglobulin ----------- multiple myeloma