Cancer 3-4: Carcinogenic Agents

Gamma rays are a type of electromagnetic radiation with very short wavelengths and high energy, making them highly penetrating.

Sieverts (Sv) are the units used to measure the biological damage caused by radiation exposure, factoring in both the type of radiation and its energy.

High LET radiation, like alpha particles, deposits energy densely along its path, causing more double-strand breaks in DNA. This leads to more complex DNA damage, including translocations and deletions.

Linear Energy Transfer (LET) describes the rate at which a radiation source deposits energy as it passes through matter. Higher LET means more energy deposited per unit distance.

Alpha particles consist of two protons and two neutrons, essentially a helium nucleus. They are highly ionizing and have a short range in matter.

Radiation damage is primarily measured by the extent of DNA damage it causes. Double-strand breaks in DNA are particularly dangerous, as they are difficult to repair accurately.

Rous Sarcoma Virus (RSV) contains an oncogene called v-src, which is a mutated form of a normal cellular gene (c-src). This mutated gene can lead to uncontrolled cell growth and cancer development.

The E6 protein encoded by HPV binds to the p53 tumor suppressor protein, marking it for degradation. This leads to reduced control over cell proliferation, allowing uncontrolled cell growth and cancer development.

Epstein–Barr Virus (EBV) is a herpesvirus that is implicated in various cancers, including Burkitt's Lymphoma and Nasopharyngeal Carcinoma. It can cause chromosomal translocations in B lymphocytes, leading to uncontrolled growth.

Helicobacter pylori, a bacterium that commonly infects the stomach, causes chronic infections. This chronic inflammation and DNA damage can lead to the development of gastric cancer.

The HTLV-1 tax protein interferes with normal cell cycle control, leading to aberrant cell proliferation. It activates the expression of genes that promote cell growth and inhibit the cell cycle.

During the immune response to Hepatitis B Virus (HBV), DNA repair mechanisms can sometimes make mistakes, leading to mutations. These mutations can be oncogenic, contributing to the development of liver cancer.

Tumor suppressor proteins play a critical role in controlling cell growth and preventing cancer. They ensure orderly cell division, repair DNA damage, and induce cell death when necessary.

Loss of heterozygosity (LOH) occurs when one allele of a gene is lost, and the other allele, which may still be functioning normally, is then silenced or inactivated. This can lead to tumor development by removing the protective function of both alleles.

Oxidative stress, a process involving reactive oxygen species (ROS), can damage DNA through various mechanisms, including oxidative respiration and lipid peroxidation. This damage can lead to mutations and ultimately cancer.

A typical mammalian cell experiences around 10^4 to 10^6 DNA damage events per day. These damage events can range from small base modifications to double-strand breaks.

Ionizing radiation, such as X-rays and gamma rays, directly interacts with DNA, causing oxidation of DNA bases. This damage can lead to mutations and cancer.

When 8-oxo-guanine, an oxidized form of guanine, is mispaired with adenine during DNA synthesis, it leads to a G → T transversion mutation.

G → T transversions are the most common type of UV-induced mutation seen in skin cancer. This occurs because UV radiation can cause the formation of pyrimidine dimers, which are often incorrectly repaired.

Failure to repair DNA damage after exposure to high levels of UV radiation can lead to mutations accumulating in cells. This can result in the inactivation of tumor suppressor genes and the activation of oncogenes, ultimately leading to cancer.

Chemical carcinogens typically exert their carcinogenic effects by directly binding to DNA bases, forming adducts. These adducts can disrupt DNA replication, cause mutations, and ultimately lead to cancer.

Cytochrome P450 enzymes are a family of enzymes that play a role in the metabolism of various compounds, including chemical carcinogens. Some chemical carcinogens are activated by these enzymes to form more reactive metabolites that are more likely to bind to DNA and cause cancer.

Benzo[a]pyrene, a polycyclic aromatic hydrocarbon found in cigarette smoke, is a major carcinogenic compound. It is metabolized to a reactive epoxide, which can bind to DNA and cause mutations.

Alkylation of the O6 position of guanine can lead to a G → T transversion mutation during DNA replication. This type of mutation is often associated with exposure to alkylating agents, which can be found in some industrial chemicals and tobacco smoke.

DNA tumor viruses, such as HPV and Epstein-Barr virus, insert their genetic material into the host genome, potentially disrupting the expression of tumor suppressor genes or activating oncogenes.

The Epstein-Barr virus (EBV) is a herpesvirus known to cause Burkitt's lymphoma, a type of cancer that affects the immune system.

The retinoblastoma protein (Rb) acts as a cell cycle regulator, particularly at the G1 checkpoint. It binds to E2F transcription factors, preventing the transcription of genes necessary for the transition from G1 to S phase.

Inherited retinoblastoma often involves a mutation that leads to the duplication of identical mutations. This is known as mitotic exchange, and results in two copies of the mutated gene.

Phosphorylation of the retinoblastoma protein (Rb) leads to a conformational change that releases the E2F transcription factor. This allows E2F to activate genes required for cell cycle progression, leading to the transition from G1 to S phase.

Individuals with germline mutations in the retinoblastoma gene typically develop retinoblastoma tumors at a young age, often before the age of 5. This is because the mutation is present from the start of their lives.

The cyclin D/Cdk4 complex plays a crucial role in regulating the transition from the G1 phase to the S phase of the cell cycle. Cyclin D binds to Cdk4, activating it and promoting cell cycle progression.

Tumor suppressor genes are genes that normally function to control cell growth and prevent cancer. Mutations in these genes can lead to increased risk of cancer development.