Which of the following stages is the carcinogen irreversible?
A. Progression stage
B. Initiation stage
C. Regression stage
D. Promotion stage
Correct Answer: A. Progression stage
Progression stage is the change of tumor from the preneoplastic state or low degree of malignancy to a fast-growing tumor that cannot be reversed. Tumor progression comprises the expression of the malignant phenotype and the tendency of malignant cells to acquire more aggressive characteristics over time. Also, metastasis may involve the ability of tumor cells to secrete proteases that allow invasion beyond the immediate primary tumor location. A prominent characteristic of the malignant phenotype is the propensity for genomic instability and uncontrolled growth.
Option B: Initiation is the first step in the two-stage model of cancer development. Initiators cause irreversible changes to DNA that increase cancer risk. The early concept of tumor initiation indicated that the initial changes in chemical carcinogenesis are irreversible genetic damage. However, recent data from molecular studies of preneoplastic human lung and colon tissues implicate epigenetic changes as an early event in carcinogenesis.
Option C: There is no regression stage in the development of cancer. Malignant conversion is the transformation of a preneoplastic cell into one that expresses the malignant phenotype. This process requires further genetic changes. The total dose of a tumor promoter is less significant than frequently repeated administrations, and if the tumor promoter is discontinued before malignant conversion has occurred, premalignant or benign lesions may regress.
Option D: The promotion stage is considered to be a relatively lengthy and reversible process in which actively proliferating preneoplastic cells accumulate. Tumor promotion comprises the selective clonal expansion of initiated cells. Because the accumulation rate of mutations is proportional to the rate of cell division, or at least the rate at which stem cells are replaced, clonal expansion of initiated cells thus, produces a larger population of cells that are at risk of further genetic changes and malignant conversion.