Molecular Mechanisms in Cancer Biology

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which type of radiation exposure is known to cause DNA damage through the generation of oxygen free radicals?

Electromagnetic radiation (correct)

Beta particles

Alpha particles

Neutrons

Which human tissue is considered to be the most sensitive to ionizing radiation?

Thyroid gland

Bone marrow (correct)

Breast tissue

Lungs

What was the predicted long-term impact on cancer cases as a result of the Chernobyl disaster?

70,000 cancer cases by 2065

100,000 cancer cases by 2065

40,000 cancer cases by 2065 (correct)

15,000 cancer cases by 2040

Which of the following statements about children undergoing CT scans is true?

The risk of brain tumors increases significantly after a certain number of scans. Signup and view all the answers

How might normal cells in a radiation treatment field be negatively affected?

They may develop cancer-promoting DNA damage. Signup and view all the answers

What role does DNA hypermethylation typically play in tumor suppressor genes?

It causes aberrant silencing of these genes without altering DNA sequences. Signup and view all the answers

How does TET2 enzyme activity vary under certain physiological conditions?

It shows increased activity in hyperglycemia. Signup and view all the answers

Which statement best describes the effect of post-translational histone modifications?

They can either open chromatin for gene expression or close it for silencing. Signup and view all the answers

What is the relationship between stem cell divisions and cancer risk according to the information provided?

A higher number of stem cell divisions correlates with an increased risk of cancer due to methylation changes. Signup and view all the answers

What is the general status of cytosine methylation in human adult cells?

70-80% of CpGs are methylated. Signup and view all the answers

What factors contribute to altered methylation patterns and histone modifications in cancers?

Age and environmental exposures, along with mutations in epigenetic modifier genes. Signup and view all the answers

Which of the following best explains why different organs and tissues function distinctively despite having the same DNA?

The variation in function is a result of histone modifications and DNA methylation patterns. Signup and view all the answers

What outcome can result from aberrant gene expression in cancer cells?

Increased tumor-cell heterogeneity and improved survival. Signup and view all the answers

What is a characteristic of a promoter in carcinogenesis?

It stimulates cell proliferation. Signup and view all the answers

Which type of cancer is most commonly associated with alkylating agents?

Acute myeloid leukemia Signup and view all the answers

What role do polymorphisms in cytochrome P-450 enzymes play in cancer susceptibility?

They increase susceptibility to carcinogens. Signup and view all the answers

Which type of UV radiation is primarily responsible for inducing cutaneous tumors?

UVB Signup and view all the answers

Which of the following best describes the effect of chronic inflammation on cancer risk?

It is associated with chronic wound repair and increases cancer risk. Signup and view all the answers

What type of skin cancer is linked with intense intermittent exposure to UV radiation?

Melanoma Signup and view all the answers

How do pyrimidine dimers affect DNA?

They distort the DNA helix and prevent proper pairing. Signup and view all the answers

Which mechanism characterizes the role of microRNAs in gene expression?

Base-pairing with complementary sequences of mRNA Signup and view all the answers

Which of the following is true about Sjögren syndrome and its cancer risk?

It increases the risk of MALT lymphoma significantly. Signup and view all the answers

What type of carcinogens require metabolic conversion to exert their effects?

Indirect-acting carcinogens Signup and view all the answers

What is the effect of the UVC radiation on cancer risk?

It is filtered out by the ozone layer and does not reach the ground. Signup and view all the answers

What is a characteristic feature of Aflatoxin B1 induced hepatocellular carcinoma?

Characterized by p53 R249S mutation Signup and view all the answers

What factors contributed to the historical increase in breast cancer incidence in the 18th century?

Hormonal factors and lifestyle changes. Signup and view all the answers

Which of the following statements regarding the initiation of chemical carcinogenesis is true?

Genetic alterations due to initiation are permanent and irreversible Signup and view all the answers

How do direct-acting carcinogens differ from indirect-acting carcinogens?

Indirect-acting carcinogens require metabolic processing to become active. Signup and view all the answers

What is a consequence of mutations in the RAS or TP53 genes?

Selective growth advantages for the cell Signup and view all the answers

Which aspect of chemical carcinogens is primarily categorized as 'promotion'?

Enhancing the proliferation of already initiated cells Signup and view all the answers

What defines chemical initiators of carcinogenesis?

They require no metabolic activation to exert effects Signup and view all the answers

Which statement accurately reflects the role of carcinogens in cancer development?

Cigarette smoke significantly increases mutational burden in lung cancer. Signup and view all the answers

Which virus is predominantly associated with hepatocellular carcinoma?

Hepatitis C Virus (HCV) Signup and view all the answers

Which of the following is not a consequence of chronic Helicobacter pylori infection?

Pulmonary fibrosis Signup and view all the answers

Which state is least likely to result from decreased immune surveillance in immunocompromised patients?

Enhanced detection of abnormal cells Signup and view all the answers

What is the significance of Class I MHC antigen processing in the context of cancer?

It is essential for the destruction of abnormal cells by CD8+ T-cells. Signup and view all the answers

Which of the following infectious agents has a recognized link to carcinogenesis?

Hepatitis B Virus (HBV) Signup and view all the answers

Which type of cancer is not typically associated with immunocompromised states?

Gastric adenocarcinoma Signup and view all the answers

Which chronic condition is recognized for its pro-carcinogenic effect due to inflammation?

Chronic hepatitis Signup and view all the answers

In the context of cancer risk, which factor is most relevant in immunosuppressed individuals?

Impaired immune response to tumor antigens Signup and view all the answers

Study Notes

DNA Hypermethylation and Demethylation

May lead to silencing of tumor suppressor genes without altering DNA sequence
May lead to over-expression of oncogenes without altering DNA sequence
CpG refers to cytosine-phosphate-guanine, a common site for methylation
TET2 enzyme is involved in demethylation and is more potent in hyperglycemia
High blood glucose levels are linked to higher cancer susceptibility

Post-translational Histone Modifications

These modifications can alter chromatin structure, promoting gene expression (open chromatin) or gene silencing (closed chromatin)
Lysine rich histone tails are frequent sites for post-translational changes
Histone acetylation is associated with an open, active chromatin state
Histone methylation has more complex and diverse effects on gene expression

microRNAs

MicroRNAs (miRNAs) are small RNA molecules (20-23 nucleotides) that regulate gene expression
miRNAs bind to complementary sequences on mRNA molecules, inhibiting translation into protein
This can lead to silencing of tumor suppressor genes

DNA Methylation Patterns in Cancer

Cancer cells often exhibit widespread alterations in DNA methylation patterns and histone modifications, resulting in aberrant gene expression
Epigenetic modifiers, such as environmental exposures, aging, and genetic mutations in epigenetic modifier genes, contribute to increased, random gene expression in cancer cells
This contributes to tumor heterogeneity and survival

Chemical Carcinogenesis

Chemical carcinogens can directly damage DNA or enhance cell proliferation
Mutations are generally random and may occur in critical genes such as RAS or TP53, leading to growth advantages and increased risk of malignant transformation
Mutations can occur in "hotspots" due to the structure of specific carcinogens
Aflatoxin B1, a common food contaminant, increases the risk of hepatocellular carcinoma, particularly in regions where it is prevalent

Initiators and Promoters

Initiation involves a permanent, irreversible genetic alteration caused by a chemical carcinogen, necessary but not sufficient for tumor formation
Promotion refers to the stimulation and alteration of an initiated cell by a chemical carcinogen, leading to reversible changes and not carcinogenic without prior initiation

Initiators - Direct and Indirect

Direct-acting carcinogens do not require metabolic conversion to become carcinogenic, usually weaker carcinogens
Some direct-acting carcinogens are used in chemotherapy
Indirect-acting carcinogens require metabolic conversion of a pro-carcinogen to become carcinogenic

Polycyclic Hydrocarbons

Polycyclic hydrocarbons are present in fossil fuels, tobacco smoke, and grilled meats
These carcinogens are metabolized in the liver by cytochrome P-450-dependent enzymes
Polymorphisms in genes encoding these enzymes can influence cancer susceptibility

Promoters

Promoters stimulate cell proliferation without being mutagenic
Promoter action in an initiated cell leads to clonal proliferation and increased risk of further mutations
Estrogen is an example of a promoter

Chronic Inflammation

Chronic inflammation is associated with increased risk of cancer due to increased cell division and regeneration during wound repair
Examples include inflammatory bowel disease and Sjögren syndrome

Stem Cell Divisions

Normal stem cell divisions can function as a promoter, contributing to the accumulation of mutations

Radiation Carcinogenesis

UV and ionizing radiation are both carcinogenic
UV Radiation is responsible for skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma
Ionizing Radiation damages DNA through oxygen free radicals, can lead to cancer development

Radiation Carcinogenesis - Sensitivity

Different tissues have different sensitivities to radiation
Bone marrow is most sensitive, followed by the thyroid in young people, and then breast, lungs, and salivary glands
Frequent CT scans are associated with increased risk of leukemia and brain tumors in children

Microbial Carcinogenesis

Hepatitis B and C viruses (HBV, HCV) are responsible for 70-85% of hepatocellular carcinoma cases worldwide, particularly in areas where HBV is endemic
Helicobacter pylori infection is associated with increased risk of gastric ulcers, gastric adenocarcinoma, and MALT lymphoma due to sustained inflammation

Cancer and Immunosuppression

Immunodeficient states increase the risk of cancer due to decreased immune surveillance
Immune surveillance involves the immune system's ability to identify and destroy abnormal cells
Antigens in tumor cells are less likely to elicit an immune response in immunosuppressed individuals, creating a favorable environment for tumorigenesis
MHC I antigen processing pathway is critical for immune surveillance, allowing cytotoxic T-cells to recognize and destroy abnormal cells.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the intricate roles of DNA hypermethylation, histone modifications, and microRNAs in cancer biology. This quiz delves into how these molecular processes influence gene expression and cancer susceptibility. Test your knowledge on these critical topics in molecular genetics.