Carcinogens and Oncogenes — Revision Notes

⚡ 30-Second Revision

Carcinogens — Agents causing cancer (physical, chemical, biological).

- Physical: UV radiation ($ightarrow$ pyrimidine dimers, skin cancer); Ionizing radiation ($ightarrow$ DNA breaks, various cancers). - Chemical: Tobacco smoke ($ightarrow$ PAHs, lung cancer); Aflatoxins ($ightarrow$ liver cancer); Asbestos ($ightarrow$ mesothelioma). - Biological: HPV ($ightarrow$ cervical cancer, inactivates p53/Rb); HBV/HCV ($ightarrow$ liver cancer); *H. pylori* ($ightarrow$ stomach cancer).

Proto-oncogenes — Normal genes, regulate cell growth ('accelerator').
Oncogenes — Mutated/overexpressed proto-oncogenes, cause uncontrolled growth ('stuck accelerator').
Activation Mechanisms — Point mutation (*RAS*), gene amplification (*HER2*), chromosomal translocation (*BCR-ABL*), viral insertion.
Tumor Suppressor Genes (TSGs) — Inhibit growth ('brakes'), repair DNA (e.g., *p53*, *Rb*). Inactivation contributes to cancer.

2-Minute Revision

Carcinogens are agents that initiate or promote cancer by damaging DNA or disrupting cellular processes. They are categorized into physical (e.g., UV radiation causing skin cancer, ionizing radiation causing DNA breaks), chemical (e.

g., tobacco smoke leading to lung cancer, aflatoxins causing liver cancer), and biological (e.g., Human Papillomavirus (HPV) causing cervical cancer by inactivating tumor suppressor genes p53 and Rb, Hepatitis B/C viruses causing liver cancer).

Proto-oncogenes are normal genes that regulate cell growth and division; they are essential for healthy cell function. When proto-oncogenes undergo specific genetic alterations, they transform into oncogenes.

These oncogenes act as 'gain-of-function' mutations, constantly signaling cells to divide uncontrollably. Common mechanisms of oncogene activation include point mutations (e.g., in the *RAS* gene), gene amplification (e.

g., *HER2/neu* in breast cancer), and chromosomal translocations (e.g., *BCR-ABL* fusion gene in CML). The development of cancer typically involves the accumulation of such oncogene activations along with the inactivation of tumor suppressor genes.

5-Minute Revision

Cancer is fundamentally a disease of uncontrolled cell proliferation, stemming from genetic alterations. Carcinogens are external agents that induce these alterations. They can be physical, such as UV radiation from sunlight, which causes specific DNA damage like pyrimidine dimers leading to skin cancers, or ionizing radiation (X-rays, gamma rays) that cause DNA strand breaks.

Chemical carcinogens are numerous, including polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke (linked to lung cancer), aflatoxins from fungal contamination (a potent liver carcinogen), and asbestos (causing mesothelioma).

These often form DNA adducts or induce mutations. Biological carcinogens are primarily viruses like HPV (cervical cancer, by inactivating p53 and Rb), HBV/HCV (liver cancer, via chronic inflammation), and EBV (lymphomas).

Some bacteria, like *Helicobacter pylori*, also act as carcinogens for stomach cancer.

Internally, proto-oncogenes are normal cellular genes that act as 'accelerators' for cell growth, division, and differentiation. They are crucial for normal development. However, when a proto-oncogene undergoes a 'gain-of-function' mutation, it transforms into an oncogene, becoming a hyperactive accelerator that drives uncontrolled cell proliferation. Key mechanisms of this activation include:

1
Point Mutation — A single nucleotide change, as seen in the *RAS* gene, leading to a constitutively active protein.
2
Gene Amplification — Multiple copies of the gene are produced, resulting in overexpression of the protein, like *HER2/neu* in breast cancer.
3
Chromosomal Translocation — A segment of DNA moves, often creating a fusion gene (e.g., *BCR-ABL* in CML) or placing a proto-oncogene under a strong promoter.
4
Viral Insertion — Viral DNA integrates near a proto-oncogene, activating its expression.

The development of cancer is a multi-step process involving the accumulation of these oncogene activations, often coupled with the inactivation of tumor suppressor genes (like *p53* and *Rb*), which normally act as cellular 'brakes' and DNA repair mechanisms. Understanding these concepts is vital for NEET, emphasizing specific examples and their associated mechanisms.

Prelims Revision Notes

Carcinogens and Oncogenes: NEET Quick Facts

I. Carcinogens (Cancer-Causing Agents)

Definition — Substances/agents that cause or promote cancer by damaging DNA or disrupting cell processes.
Types & Examples:

* Physical Carcinogens: * UV Radiation: From sunlight. Causes pyrimidine dimers in DNA. Leads to skin cancers (basal cell, squamous cell, melanoma). * Ionizing Radiation: X-rays, gamma rays, alpha particles.

Causes DNA strand breaks, chromosomal aberrations. Linked to leukemia, thyroid cancer, etc. * Asbestos: Fibrous mineral. Causes chronic inflammation. Linked to mesothelioma (pleural/peritoneal lining cancer) and lung cancer.

* Chemical Carcinogens: * Tobacco Smoke: Contains Polycyclic Aromatic Hydrocarbons (PAHs, e.g., Benzo[a]pyrene), nitrosamines. Major cause of lung cancer, oral, esophageal, bladder cancer.

PAHs form DNA adducts. * Aflatoxins: Produced by *Aspergillus flavus* (fungus) on contaminated food (peanuts, corn). Potent liver carcinogen (hepatocellular carcinoma). Causes G>T mutations in *p53*.

* Benzene: Industrial solvent. Linked to leukemia. * Nitrosamines: Formed from nitrites in processed foods. Linked to gastric, esophageal cancer. * Biological Carcinogens (Oncogenic Microbes): * Viruses: * Human Papillomavirus (HPV): High-risk types (16, 18).

Primary cause of cervical cancer. Viral proteins E6 & E7 inactivate tumor suppressor proteins p53 & Rb. * Hepatitis B Virus (HBV) & Hepatitis C Virus (HCV): Chronic infection leads to liver cancer (hepatocellular carcinoma) via chronic inflammation and viral protein effects.

* Epstein-Barr Virus (EBV): Linked to Burkitt's lymphoma, nasopharyngeal carcinoma. * Human T-lymphotropic Virus Type 1 (HTLV-1): Causes Adult T-cell Leukemia/Lymphoma (ATLL). * Bacteria: * *Helicobacter pylori*: Chronic infection linked to stomach cancer (gastric adenocarcinoma) and gastric MALT lymphoma.

* Parasites: * *Schistosoma haematobium*: Linked to bladder cancer.

II. Oncogenes

Proto-oncogenes — Normal genes regulating cell growth, division, differentiation. Act as cellular 'accelerators'.
Oncogenes — Mutated or overexpressed proto-oncogenes. Lead to uncontrolled cell growth (gain-of-function).
Mechanisms of Activation:

1. Point Mutation: Single nucleotide change. E.g., *RAS* gene (Glycine to Valine at codon 12) $ightarrow$ constitutively active RAS protein. Found in pancreatic, colorectal, lung cancers. 2. Gene Amplification: Increase in gene copies.

E.g., *HER2/neu* (ERBB2) amplification $ightarrow$ overexpression of receptor tyrosine kinase. Found in breast, gastric cancers. 3. Chromosomal Translocation: Exchange of genetic material between chromosomes.

E.g., Philadelphia chromosome (t(9;22)) $ightarrow$ *BCR-ABL* fusion gene $ightarrow$ constitutively active tyrosine kinase. Causes Chronic Myelogenous Leukemia (CML). 4. Viral Insertion: Viral DNA integrates near a proto-oncogene, activating its expression.

III. Tumor Suppressor Genes (TSGs)

Function — Act as cellular 'brakes'. Inhibit cell growth, repair DNA, induce apoptosis. (Loss-of-function contributes to cancer).
Examples — *p53* (guardian of the genome), *Rb* (retinoblastoma protein).

IV. Key Concepts for NEET:

Distinguish proto-oncogene vs. oncogene vs. tumor suppressor gene.
Memorize specific carcinogen-cancer associations.
Understand the four main mechanisms of oncogene activation with examples.

Vyyuha Quick Recall

To remember the main types of carcinogens: Physical, Chemical, Biological.

Physical: Radiation (UV, Ionizing) Chemical: Tobacco, Asbestos, Aflatoxins Biological: Viruses (HPV, Hep B/C), Bacteria (*H. pylori*)

Think: Please Call Back Regarding The Association And Viral Bacteria. (P-C-B, R-T-A-A, V-B)