carcinogenesis Flashcards
(37 cards)
It is a phenomenon of gene alteration, which may result from the interaction of ultimate carcinogens with DNA in the target cell.
Initiation
It refers to a phenomenon of gene activation in which the latent altered phenotype of the initiated cell becomes expressed through selection and clonal expansion
promotion
It refers to a phenomenon of gene activation in which the latent altered phenotype of the initiated cell becomes expressed through selection and clonal expansion
promotion
It is the last irreversible stage of multistage carcinogenesis, which usually develops from the cells in the stage of promotion.
Progression
A chemical is transformed into a DNA-reactive metabolite (ultimate carcinogen).
Metabolic Conversion to an Ultimate Carcinogen
The ultimate carcinogen binds to DNA, causing structural damage (e.g., mutations, adducts).
DNA Interaction and Structural Alteration
Cellular repair mechanisms may reverse the damage, but if unsuccessful, mutations persist.
DNA Repair Attempts
When the damaged cell divides, the mutation becomes permanently fixed in the genome
Cell Proliferation and Mutation Fixation
It is the second stage in multistage carcinogenesis, characterized by the activation of gene expression that leads to the clonal expansion of initiated cells.
Unlike initiation, promotion does not involve direct DNA damage but rather alters gene expression patterns, allowing preneoplastic cells to proliferate
PROMOTION
ASPECTS OF PROMOTION
Reversible
Non Genotoxic
Long Duration
Dose Dependent
Dependent on continuous exposure to promoting agents; lesions may regress if
exposure stops.
Reversible
Tumor promoters do not directly damage DNA but modify cellular signaling pathways
Non Genotoxic
Can persist for decades in humans.
Long Duration
Exhibits threshold effects (sigmoid dose-response curve)
Dose-Dependent
Promoters stimulate the proliferation of initiated cells, giving them a growth advantage.
Clonal Expansion of Initiated Cells
Promoters modify cell signaling pathways, leading to changes in:
-Growth factors (e.g., EGFR signaling).
-Anti-apoptotic mechanisms (e.g., Bcl-2 upregulation).
-Inflammatory responses (e.g., NF-κB activation
Altered Gene Expression
Many promoters (e.g., phenobarbital, TCDD) suppress programmed cell death, allowing
preneoplastic cells to survive.
Inhibition of Apoptosis
Withdrawal of promoters can lead to apoptosis-induced regression of preneoplastic
lesions.
Reversibility and Regression
It represents the final, irreversible stage of multistage carcinogenesis,
developing from previously promoted cells. This stage is characterized by
increasing genomic instability and karyotypic evolution, leading to morphologically
detectable changes in cellular structure.
Progression
Key Aspects of Progression
Irreversible genetic damage (distinct from reversible promotion)
Karyotypic instability (abnormal chromosome structure/number)
Emergence of invasive/metastatic potential
Clinical cancer manifestation
Chemicals that drive transition from promotion to progression
Progressor Agents
The dose of a substance that causes death in 50% of a population of test animals.
LD50 (Lethal Dose 50):
The concentration of a substance in the environment that causes death in 50% of a
population of test organisms.
LC50 (Lethal Concentration 50):