Cell that is transformed .
Recognized by population of abnormal cells within the
normal tissue causing destruction of normal cell
population & behave like parasite.
A simplified hypothesis for development of cancer
Inactive anti-oncogenes Diminish
factors( physical and
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
Loss of anchorage.
Causes of cancer
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)
• 80% of cancer caused by chemicals
• Organic eg. benzo pyrine,
• Organic eg. benzo pyrine,
Inorganic eg. Cadmium , Arsenic
How carcinogens enter in the body ?
Occupation ==== Asbestos, benzene
Diet --------------- Aflatoxin produced by fungus
(Aspergillus flavous) contamination with peanuts.
Life style-----------Cigarette smoking
Two types ---- Direct
Role of initiator & promoter
Potential tumor cells
Release & migration of cancer cells
• Metabolites of Tyrosine :
Phenol & cresol
Tryptophan: Indol & Indol
• Tumor of Bladder
• Tumor of Gastrointestinal
Mechanism of action of chemical carcinogen
Pro -carcinogen proximate carcinogen
Electrophiles (deficient in
Enzyme responsible for activation-----Cytochrome P450
Some chemical carcinogens
• Polycyclic aromatic
• Azo dyes (Aromatic amines)
• Various drugs ( alkylating &
• Aflatoxins(fungus Aspergillus
• Benzo pyrene present in
• An aniline azo dye Used in rubber
• Synthesized in gut from ingested
nitrites or derived from digested
proteins: gastric cancer
• Mold.-- potent hepatic
Genes of viral origin which causes transformation of
Rous 1911 ------ got Nobel prize in 1966
RNA –mostly of retroviruses
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
Mechanism of infective retrovirus formation
C DNA or
Becomes a part of host DNA
Process of integration of viral genes into cellular DNA
Mechanism by which proto-oncogene become oncogene
Proto-oncogene is the normal non mutated cellular
analog of oncogene.
e.g. Avian leukemia virus
In chronic granulocytic leukemia: Translocation between 9th and 22nd chromosome.
Burkitt’s Lymphoma: chromosomal translocation
8 8 8
14 14 14
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.
5. Single point mutation
V-ras oncogene --------murine retrovirus
polypeptide related to G protein
modulates the activity
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
Mechanism of action of oncogenes:
1. Autocrine mechanism--- oncogene product is growth factor*
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.
Tumor suppressor genes Or
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
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
Marker Associated cancer(s)
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
Calcitonin ------------CA of medullary thyroid
Catecholamines and their
metabolites (VMA) -------------Neuroblastoma
Prosthetic acid phosphatase ------------ Prostate cancer
Neuron specific enolase ------------Neuroblastoma
Alkaline phosphatase(ALP) ------------Bone secondary's
Immunoglobulin ----------- multiple myeloma