FACULTY OF PHYSICAL SCIENCE.
DEPARTMENT OF ENVIRONMENTAL SCIENCES.
ASSIGNMENT
COURSE TITLE: Principles of Toxicology
COURSE CODE: EMT 413
QUESTION: HOW CELL INJURY MANIFEST THROUGH
CARCINOGENESIS
BY: GROUP 1
NAMES [Link]
MOHAMMED DAYYABU FSC/EMT/22/2002
IDRIS ADAM SHEHU FSC/EMT/20/1027
ADAMU IBRAHIM FSC/EMT/20/1011
UMAR BALA AHMAD FSC/EMT/20/1128
SANI SAFIYANU FSC/EMT/20/1034
ABDULLAHI ADAMU AHMAD FSC/EMT/20/1092
UMMI OMINISI FSC/EMT/20/1065
BASHIR IBRAHIM TSOHO FSC/EMT/20/1010
AMIRA NASIR FSC/EMT/20/1013
INTRODUCTION
Cell injury is a fundamental factor in the development of cancer, as it can lead to genetic
mutations, epigenetic alterations, and disruptions in normal cellular function. The process of
carcinogenesis is complex and multifaceted, involving a series of genetic and epigenetic
changes that ultimately transform normal cells into cancer cells. To understand how cell injury
manifests in carcinogenesis is vital for developing effective strategies for cancer prevention,
early detection, and treatment. In this topic we will explore the mechanism of cell injury, the
consequences of cell injury in carcinogenesis and other pathways involved in this process.
DEFINITION OF TERMS
Cell injury: occurs when cells are exposed to severe stress that disrupts their
normal functioning, leading to reversible or irreversible damage.
Carcinogenesis: also called oncogenesis or tumorigenesis, is the formation of
a cancer, where normal cells are transformed into cancer cells.
Cancer: is a complex disease characterized by the uncontrolled growth and
proliferation of abnormal cells, which can invade and damage surrounding tissues
and organs. Cancer development involves a series of genetic and epigenetic
alterations that disrupt normal cellular function and regulation.
ROLES OF CELL DIVISION IN CANCER FORMATION
Cell division plays a crucial role in cancer formation:
There are two main types of cell division:
1. Mitosis
Mitosis is a type of cell division that results in two daughter cells with the same number of
chromosomes as the parent cell. It's essential for:
- Growth and development
- Tissue repair
- Cell replacement
2. Meiosis
Meiosis is a type of cell division that occurs in reproductive cells (gametes) and results in four
daughter cells with half the number of chromosomes as the parent cell. It's crucial for:
- Genetic diversity
- Sexual reproduction
These two types of cell division play distinct roles in maintaining tissue homeostasis and
ensuring the continuation of species.
Mitosis in Cancer Formation
1. Uncontrolled cell growth: Cancer cells exhibit uncontrolled mitosis, leading to
tumor growth.
2. Genetic mutations: Errors during mitosis can lead to genetic mutations,
contributing to cancer development.
3. Tumor progression: Rapid mitosis in cancer cells can drive tumor progression
and metastasis.
Meiosis in Cancer Formation
1. Germline mutations: Mutations in germline cells (sperm or egg cells) can be
passed on to offspring, increasing cancer risk.
2. Hereditary cancers: Some cancers are caused by inherited mutations in genes
involved in meiosis or DNA repair.
Key Implications
1. Genomic instability: Both mitosis and meiosis can contribute to genomic
instability, a hallmark of cancer.
2. Cancer development: Understanding the role of mitosis and meiosis in cancer
formation can inform cancer prevention and treatment strategies.
Mechanism of Cell Injury Through Carcinogenesis
Carcinogenesis is the process by which normal cells transform into cancer cells due to
accumulated genetic and epigenetic alterations. Cell injury plays a crucial role in initiating and
promoting carcinogenesis by inducing DNA damage, oxidative stress, chronic inflammation, and
dyregulation of cellular repair mechanisms.
1. INITIATION:
DNA DAMAGE AND MUTATIONS
The first step in carcinogenesis is (initiation) where normal cells acquire genetic mutations that
confer a growth advantage.
CAUSES OF DNA DAMAGE:
- Chemical Carcinogens (e.g., tobacco smoke, aflatoxin, benzene)
- These agents form DNA adducts, leading to mutations (e.g., *TP53* mutations in lung cancer).
- Physical Carcinogens (e.g., UV radiation, ionizing radiation)
- UV light causes thymine dimers, while ionizing radiation induces double-strand breaks.
- Biological Carcinogens (e.g., oncogenic viruses like HPV, HBV, EBV)
- Viral oncoproteins (e.g., HPV E6/E7) inactivate tumor suppressors (p53, Rb).
- Reactive Oxygen Species (ROS)
- Oxidative stress from inflammation or toxins causes base modifications (8-oxoguanine) and
strand breaks.
KEY MUTATIONS IN INITIATION:
- Activation of Proto-oncogenes → Oncogenes (e.g., RAS, MYC, EGFR)
- Inactivation of Tumor Suppressor Genes (e.g., TP53, RB, APC)
- Defects in DNA Repair Genes (e.g., BRCA1/2, MLH1/MSH2 in Lynch syndrome)
2. PROMOTION:
CLONAL EXPANSION OF MUTATED CELLS
After initiation, promotion involves the selective proliferation of mutated cells
due to:
- Chronic inflammation (e.g., H. pylori in gastric cancer, hepatitis in HCC)
- Inflammatory cytokines (TNF-α, IL-6) promote cell survival and proliferation.
- Hormonal stimulation (e.g., estrogen in breast cancer)
- Oxidative stress leading to further DNA damage.
Mechanisms:
- Epigenetic Changes (DNA methylation, histone modifications) silence tumor
suppressors.
- Anti-apoptotic Signals (Bcl-2 overexpression) allow survival of damaged cells.
3. PROGRESSION:
MALIGNANT TRANSFORMATION
The final stage involves progression, where preneoplastic cells acquire additional
mutations, leading to:
- Genomic instability(chromosomal translocations, aneuploidy).
- Angiogenesis(VEGF secretion).
- Invasion & Metastasis (loss of E-cadherin, MMP activation).
4. Role of Chronic Injury & Inflammation
Persistent cell injury (e.g., chronic hepatitis, GERD, smoking) leads to:
- Cyclooxygenase-2 (COX-2) upregulation → Prostaglandins promote growth.
- NF-κB activation → Pro-inflammatory cytokines sustain proliferation.
- ROS/RNS production → Further DNA damage.
TO PREVENT CARCINOGENESIS
1. Avoid exposure to carcinogens: Reduce exposure to environmental toxins, such
as tobacco smoke, pesticides, and heavy metals.
2. Maintain a healthy lifestyle: Engage in regular physical activity, eat a balanced
diet, and maintain a healthy weight.
3. Protect against UV radiation: Use sunscreen, clothing, and hats to prevent skin
damage from UV radiation.
4. Get vaccinated: Get vaccinated against viruses that can cause cancer, such as
human papillomavirus (HPV) and hepatitis B virus (HBV).
5. Avoid infections: Practice safe sex, and avoid sharing needles or other
equipment that can transmit infectious agents.
6. Screening and early detection: Participate in regular cancer screening tests,
such as mammograms, colonoscopies, and Pap tests.
CONCLUSION
Carcinogenesis is a multi-step process where cell injury (via DNA damage,
oxidative stress, and inflammation) leads to mutations in oncogenes and tumor
suppressors, followed by clonal expansion and malignant progression Chronic
injury accelerates this process by sustaining a pro-carcinogenic microenvironment.
Understanding these mechanisms is crucial for cancer prevention (e.g., reducing
carcinogen exposure) and targeted therapies(e.g., PARP inhibitors for BRCA
mutant cancers).
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