18 5-13 hypotheses of origin of neoplasia
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Mechanisms of neoplasia include monoclonal origin from a single mutated cell and field origin from multiple mutated cells in a tissue. The lag period between exposure to a carcinogen and cancer development can be over 20 years. Multiple genetic hits or mutations are believed to be required for cancer, caused by initiators like carcinogens and promoters. Factors that can cause these mutations include viruses, immune responses, and DNA mutations.
18 5-13 hypotheses of origin of neoplasia
- 1. Mechanisms & Causes of Neoplasia kj
- 2. • Hypotheses of Origin of Neoplasia • Monoclonal Origin • Field Origin • The Lag Period • Multiple Hits & Multiple Factors
- 3. Several hypotheses have been advanced to explain neoplasia • Majority in response to advances in the basic sciences current at the time. • Hypotheses of the viral cause of neoplasia coincided with the demonstration of transmission of certain animal neoplasms by ultrafiltrable agents • ROUS SARCOMA, 1908; • SHOPE PAPILLOMA, 1933; • BITTNER MILK FACTOR, 1935
- 4. Peyton Rous(1879-1970) • Isolated the Ist tumour- containing animal virus 1911 • Nobel prize in 1966
- 7. Cal West Med. 1941 October; 55(4): 173–174.
- 8. • Immunologic hypotheses after experiments involving tumor transplantation in animals (Ehrlich, 1908; immune surveillance, Burnet, 1950s) • • DNA mutations as a (Watson and Crick, 1950s)
- 9. Two general types of origins proposed for neoplasms Monoclonal Origin • The initial neoplastic change affects a single cell, multiplies & => the neoplasm. • Neoplasms of B lymphocytes (B-cell lymphomas and plasma-cell myelomas) that produce immunoglobulin
- 12. Field Origin • A carcinogenic agent acting on a large number of similar cells may produce a field of potentially neoplastic cells. • Neoplasms may then arise from one or more cells within this field. • In many cases the result is several discrete neoplasms, each of which derives from a separate clonal precursor. • The field change may be regarded as the first of 2 or more sequential steps that lead to overt cancer
- 13. Multifocal (neoplastic field) neoplasms occur • Skin, Urothelium, Liver, Breast, & Colon. • Alert the clinician • Cancer in one breast carries a risk of cancer in the opposite breast that is about 10 times higher than that of the general population
- 14. The Lag Period • Interval between exposure and development of the neoplasm • A constant feature of all known agents that cause neoplasms • Hiroshima and Nagasaki, the largest number of cases of leukemia occurred about 10 years • Some cancers developed as late as 20 years afterward.
- 15. • In shipyard workers exposed to asbestos during world war II, neoplasms attributed to asbestos were rare within 15 years of exposure. • However, new cases were identified through the 1970s even though exposure stopped in the 1940s. • In utero exposure to DES may give rise to vaginal cancer 15 or more years after birth. • Difficulty in identifying carcinogenic agents for common neoplasms.
- 16. Multiple Hits & Multiple Factors • Knudson proposed that carcinogenesis requires two hits • The first event is initiation, and the carcinogen causing it is the initiator. • The second event, which induces neoplastic growth, is promotion, and the agent is the promoter. • The period between the first hit and the development of clinically apparent cancer is the lag period.
- 18. It is now believed • Multiple hits occur (five or more), that multiple factors may cause these hits, • Each hit produces a change in the genome of the affected cell that is transmitted to its progeny (ie, the neoplastic clone).
- 20. Multi-hit phenomenon with sequential genetic changes leading to carcinoma of the colon