2. CARCINOGENESIS- PATHOGENESIS OF
CANCER
• a normal cell is transformed into a malignant
cell and repeatedly divides to become a cancer.
A chemical which can initiate this process is
called a chemical carcinogen.
• Two major categories of mutated genes are
1) oncogenes
2) tumor suppressor genes.
3. • Oncogenes are abnormal forms of normal genes called proto-
oncogenes that regulate cell growth. Mutation of these genes may
result in direct and continuous stimulation of the molecular
biologic pathways that control cellular growth and division.
• Tumor suppressor genes ,p53, are inherent genes that play a role
in cell division and DNA repair and are critical for detecting
inappropriate growth signals in cells.
4. P53 GENE
• p53 Gene senses DNA damage, and induces G1 arrest
and induces DNA repair process.Cell with un-repairable
DNA is directed to apoptosis by p53 gene.“P53 is a
guardian of the genome.Its loss leads to accumulation
of damaged DNA may result in malignancy” Loss of p53
is seen in virtually every type of cancer.
7. CHEMICAL CARCINOGENESIS
• Most chemical carcinogens are
procarcinogens and require
metabolic activation to form the
ultimate carcinogen
• • Balance between metabolic
activation and inactivation.
8. • Genotoxic Carcinogen: -Chemical capable of producing cancer by directly altering
the genetic material of target cells.
• DNA replication errors.
• Point mutations.
• Chromosomal aberration.
• 1 Direct carcinogens (no metabolic activation).
• - Alkylating agents
• 2 Indirect carcinogens (metabolic activation).
• Polycyclic aromatic hydrocarbons.
• Aromatic amines.
• Nitrosamines.
9.
10. RADIATION CARCINOGENESIS
• lonizing radiation -> Carcinogenesis
• can result from lionization radiation and may
develop from 2 different mechanisms;
• Direct ionization - damages DNA and other
molecules can cause direct somatic mutations
• Secondary effectors such as oxygen radicals can
be formed by ionizing radiation. Oxygen free
radicals can damage and kill cells and also
induce
11. • Radiation- Ultraviolet light
• Causes: mutation, inhibits cell division and cell
death
• MOA: formation of pyrimidine dimer
• Main source of UV light is sunlight, UV lamp
• Penetration of UV light protected by melanin
12. VIRAL ONCOGENESIS
• Viruses contribute to the pathogenesis of human
malignancies through the integration of viral genetic
elements into the host
DNA. These new genes are expressed by the host; they may
• Disrupt normal host genes required for control of cell growth
and division
13. SOME DNA VIRUSES
• Form stable associations with host cells genome.
• Papillomaviruses- Involved in the pathogenesis of warts to carcinoma.
• Epstein-Barr virus- Involved in the pathogenesis of Burkitt lymphoma
and
Hodgkin disease.
• Hepatitis B virus- Involved in the pathogenesis of liver cancer.
