DNA damage from radiation can wreak havoc on cells. When left unrepaired, it can lead to cell death, mutations, and . These effects ripple through generations of cells, potentially causing cancer and other long-term health issues.
Understanding the consequences of unrepaired DNA damage is crucial for grasping radiation's impact on our bodies. From cell cycle disruption to epigenetic changes, these effects highlight why our are so important for maintaining cellular health and preventing disease.
DNA Damage Outcomes in Irradiated Cells
Cell Death and Mutation
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Unrepaired DNA damage triggers cell death through or depending on damage extent and type
Mutations arise when damaged DNA replicates before repair alters gene expression or protein function
result from unrepaired leading to deletions, translocations, or fusions (Philadelphia chromosome in chronic myeloid leukemia)
Genomic instability emerges characterized by increased genetic alterations in subsequent cell generations
Cell Cycle Disruption and Epigenetic Changes
occurs at checkpoints preventing damaged cells from dividing until repair completion or cell death initiation (G1/S and G2/M checkpoints)
induces permanent cell cycle arrest in cells with persistent DNA damage
Epigenetic changes affect gene expression due to unrepaired DNA damage altering DNA methylation patterns (hypermethylation of tumor suppressor genes)
DNA Damage, Genomic Instability, and Carcinogenesis
Genomic Instability and Cancer Hallmarks
Unrepaired or misrepaired DNA damage leads to genomic instability increasing mutations and chromosomal aberrations
Genomic instability drives accumulation of additional mutations necessary for carcinogenesis (mutator phenotype)
Specific mutations in oncogenes or tumor suppressor genes initiate carcinogenic process (BRCA1/2 mutations in breast cancer)
Chromosomal instability causes aneuploidy and structural abnormalities commonly observed in cancer cells (trisomy 21 in acute myeloid leukemia)
Telomere Dysfunction and Epigenetic Alterations
Telomere dysfunction associated with genomic instability contributes to chromosomal fusions and breakage-fusion-bridge cycles promoting cancer progression
Epigenetic alterations from DNA damage lead to aberrant gene expression patterns potentially contributing to carcinogenesis (hypermethylation of p16 tumor suppressor gene)
Accumulation of DNA damage and genomic instability over time increases likelihood of cellular transformation and cancer development
Defective DNA Repair and Radiation Sensitivity
DNA Repair Deficiencies and Radiosensitivity
Defects in DNA repair pathways (, ) significantly increase cellular sensitivity to
Inherited DNA repair deficiency syndromes exhibit heightened radiosensitivity (, )
Impaired DNA repair accumulates unresolved DNA damage increasing likelihood of cell death or genomic instability following radiation exposure
Defective DNA repair mechanisms lower threshold for as damaged DNA more likely misrepaired or replicated with errors
DNA Repair and Cancer Treatment
Radiotherapy efficacy influenced by DNA repair capacity of tumor cells with deficient repair potentially enhancing tumor radiosensitivity
DNA repair gene polymorphisms contribute to individual differences in radiation sensitivity and cancer susceptibility ()
Understanding DNA repair mechanism status in tumors informs personalized radiotherapy strategies and predicts treatment outcomes ( in BRCA-deficient tumors)
Long-Term Effects of Radiation-Induced DNA Damage
Cellular Dysfunction and Genomic Instability
Persistent DNA damage chronically activates DNA damage response pathways altering cellular metabolism and energy allocation
Accumulating mutations from unrepaired or misrepaired DNA damage progressively impair cellular function and tissue homeostasis
Radiation-induced genomic instability transmits to daughter cells affecting function of entire cell populations or tissues long after initial exposure
Epigenetic changes alter gene expression patterns leading to long-term changes in cellular phenotype and function ( of repetitive elements)
Tissue Aging and Bystander Effects
Cellular senescence induced by persistent DNA damage contributes to tissue aging and age-related pathologies through pro-inflammatory factor secretion (senescence-associated secretory phenotype)
Radiation-induced bystander effects cause DNA damage and functional changes in non-irradiated cells amplifying long-term impact on tissue function
Chronic oxidative stress associated with radiation-induced DNA damage leads to cumulative cellular dysfunction contributing to various pathological conditions (radiation-induced fibrosis)