Carcinogenic
Agents and
Their Cellular
Interactions
Mrs. Pubudini Weerasooriya
LO
• List common direct acting and indirect acting chemical carcinogens.
• explain the mechanism by which chemical carcinogens induces cancer.
• Discuss the role of radiation in carcinogenesis.
• list oncogenic viruses and other microorganisms involved in
carcinogenesis.
• explain the mechanism by which these microorganisms induce
carcinogenesis.
• relate the carcinogenic agents to preventive, diagnostic and therapeutic
strategies of cancers caused by them.
What are Carcinogens?
➢ Cancer results from dysregulated cell growth due to
genetic and epigenetic changes.
➢ Carcinogens are agents: chemical, physical, or
biological that cause cancer by disrupting cellular
processes.
➢ Understanding how carcinogens work is essential for
cancer prevention, diagnosis, and treatment.
Types of Chemical Carcinogens
➢ Direct-acting carcinogens: No metabolic activation
needed.
Examples: Cyclophosphamide, nitrosamines.
➢ Indirect-acting carcinogens (Procarcinogens):
Require metabolic activation.
Examples: Polycyclic aromatic hydrocarbons (PAHs),
aflatoxin B1, aromatic amines.
Steps in Carcinogenesis
➢ Involves exposure to a mutagenic agent that causes permanent
DNA damage.
Initiation ➢ This stage is irreversible.
➢ Mutated cells are not yet cancerous but have the potential for
transformation.
➢ In this stage, initiated cells are exposed to promoting agents
that stimulate the growth and proliferation of these cells.
➢ Promoters do not directly cause mutations but can enhance
Promotion the survival and division of cells with mutations.
➢ This leads to the formation of pre-neoplastic lesions, which
are clusters of cells with the potential to become cancerous.
➢ Progression involves accumulation of further genetic and
epigenetic changes.
Progression ➢ Cells acquire malignant characteristics such as invasiveness
and resistance to apoptosis.
➢ The spread of cancer cells from the place where they first
Metastasis formed to another part of the body.
DNA Adduct Formation and
Mutation
• Activated carcinogens bind covalently to DNA, forming DNA adducts.
• Failure to repair adducts leads to mutations, e.g., aflatoxin B1 causes G to T
transversion in TP53.
Ionizing Radiation and
Carcinogenesis
• Sources: X-rays, gamma rays, radioactive isotopes.
• Causes double-strand DNA breaks, chromosomal aberrations.
• Associated with leukemias, thyroid and breast cancers.
• Examples: Atomic bomb survivors, Chernobyl exposure.
Non-ionizing Radiation: UV
Radiation
• UVB radiation (280–320 nm) causes pyrimidine
dimers.
• Leads to DNA replication errors and mutations.
• Commonly mutated gene: TP53 in skin cancers.
• Cancers: Basal cell carcinoma, squamous cell
carcinoma, melanoma.
Biological Carcinogens: Oncogenic
Viruses
• Viruses integrate into host genome or alter signaling.
• Mechanisms: Inactivation of tumor suppressors, chronic
inflammation, immune evasion.
Human Papillomavirus
(HPV)
• High-risk strains: HPV-16, HPV-18.
• E6 protein: Degrades p53.
• E7 protein: Inactivates Rb protein.
• Associated cancers: Cervical, anal,
oropharyngeal.
Epstein-Barr Virus (EBV)
• Infects B-cells and epithelial cells.
• Associated with Burkitt lymphoma,
Hodgkin lymphoma, nasopharyngeal
carcinoma.
• Oncogenic proteins: LMP-1 and
EBNA proteins.
Hepatitis B and C Viruses (HBV, HCV)
• Chronic infection → inflammation, cirrhosis →
cancer.
• HBx protein disrupts p53 and promotes
proliferation.
• Associated with hepatocellular carcinoma.
Human T-cell Leukemia Virus Type 1
(HTLV-1)
• RNA retrovirus causing adult
T-cell leukemia/lymphoma.
• Tax protein activates NF-κB
and IL-2 production.
• Promotes T-cell proliferation
and transformation.
Oncogenic Bacteria and
Parasites
• Helicobacter pylori → Gastric cancer,
MALT lymphoma.
• Schistosoma haematobium → Bladder
cancer.
• Opisthorchis viverrini →
Cholangiocarcinoma.
Mechanisms: Microorganisms in
Carcinogenesis
• Microorganisms induce cancer by chronic
inflammation, toxin secretion, or direct gene
activation.
• H. pylori’s CagA protein activates oncogenic
pathways.
• Parasites cause tissue damage and cytokine
dysregulation.
Diagnostic Approaches
• Molecular biomarkers: TP53
mutations (aflatoxin), EBV DNA
(nasopharyngeal carcinoma).
• Screening programs: Pap smear,
HPV DNA test, colonoscopy.
• Detection of microbial infections
linked to cancer.
Prevention of Carcinogen-Induced
Cancers
• Vaccines: HPV and HBV to prevent cervical
and liver cancers.
• Avoid tobacco, limit alcohol, reduce UV
exposure.
• Occupational safety to reduce exposure to
industrial carcinogens.
Therapeutic Strategies
• Targeted therapies: Drugs against viral oncoproteins.
• Immunotherapy: Especially in virus-associated
cancers.
• Eradication therapy: Antibiotics for H. pylori;
antiparasitic for flukes and schistosomiasis.
Conclusion
Carcinogens; whether chemical, physical, or
biological act via different mechanisms to
disrupt cellular homeostasis.
A deep understanding of these interactions
has enabled better preventive strategies,
diagnostic tools, and targeted therapies,
ultimately improving patient outcomes.
Thank You
