Module 3: Toxicology - Section 13: Occupational Carcinogenesis

TOX 13.3: Stages of Carcinogenicity - Promotion and Progression

PROMOTION:

This is the process whereby the initiated cell must undergo clonal expansion to intermediate cells.  This depends on the presence of tumour promoters acting through   "epigenetic" mechanisms  - hyperplasia, inflammation, increased DNA and protein synthesis, increased synthesis of phospholipids and prostoglandins and a series of other changes in gene expression and cellular morphology. Promoting agents do not bind to DNA themselves but their interaction with DNA produces alterations in gene expression. Promoters themselves therefore cannot produce cancer without prior initiation.

PROGRESSION:

The benign lesions produced by promotion would not lead to death. Progression in the final stages of carcinogenesis of benign clones to malignant cancer is a complex process involving a series of genetic alterations. This increased genetic instability results in acceleration of the malignant phenotypes. Invasion and metases follows. In the latter stages of progression, a selective process favours rapid evolution of the tumour cells into the most malignant form. At this stage the tumour cells develop abnormal characteristics and the ability to cross basement membranes, survive in the bloodstream, counteract immune systems and resist toxic effects of drugs and radiation.

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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