Tumour Pathology 4 and 5 Flashcards
Mitosis
Mechanism of cellular replication. A diploid cell becomes 2 diploid cells.
Cell cycle
The time interval between mitotic divisions.
G2 = preparation for mitosis and cell growth.
M = mitosis and cell division
G1 = synthesis of components required for DNA synthesis and a checkpoint.
S = DNA synthesis.
G1, S and G2 are known as the interphase.
There are approximately 25 x 10^(6) cell divisions per second.
Number of cells in body
Approximately 10^(13)
Carcinogenesis
Caused by a mutation of genetic material that upsets the normal balance between proliferation and apoptosis. Only mutations in genes regulating cell division, apoptosis and DNA repair cause a cell to lose control of proliferation.
Abnormal cell cycle
The primary defect in cancer is uncontrolled proliferation via cell cycle dysregulation
Cell pathways disrupted
- Cyclin D-pRb-E2F
- p53
- Virtually all cancers are dysregulated at G1-S because of mutation in one of four genes; Rb, CDK4, cyclin D, p16.
Aetiological cancer agents
Chemicals, radiation, oncogenic viruses, age, inherited.
How do aetiological agents cause abnormalities
The purine and pyramidine bases in DNA are critical cellular targets for damage by radiation and various oxidising and alkylating agents. Chemical carcinogens/active metabolites react with DNA to form adducts. Adduct formation at particular sites in DNA leads to the activation of oncogenes and suppression of tumour suppressor genes.
Tumour formation
More than one mutation is necessary for carcinogenesis. All sporadic cancers harbour multiple genetic abberations and abnormalities which accumulate with time. Activation of several oncogenes and loss of 2 or more anti-oncogenes occurs in most cancers.
Genetic changes in cancer
Mutations can be sporadic and/or inherited and they accumulate over time. Loss of cell cycle control leads to malignant transformation. Key regulators include; p16, cyclin D, CDK4 and Rb and are mutated in majority of cancers. Loss or mutation of p53 allows genetically damaged cells to proliferate forming malignant neoplasms.