Leon P Bignold
University of Adelaide, Australia
Title: Mechanisms of action of carcinogens for the complexities of the tumor types
Biography
Biography: Leon P Bignold
Abstract
1. The etio-pathogenesis of tumors is thought to involve somatic mutations / genomic events, but how carcinogens induce genomic events is unclear. 2. For an agent to cause a tumor, five steps are involved (1): (i) The exogenous causative factor(s) enters, or perhaps only impinges on, a somatic cell. (ii) The exogenous agent(s) act on a critical structural or biochemical target(s) in the cell. (iii) A particular function of the target is disturbed. (iv) The disturbance in the function in the target has a pro-tumor genomic effect. (v) The relevant effect(s) / genomic event(s) produce the features of the thousand or so different types of tumors – from different parent cells, but nevertheless, all from the one genome. 3. This paper discusses the pathogenesis of chemical and radiation carcinogenesis under the following headings: (i) Toxicokinetics, including at the nuclear level (1). (ii) The intranuclear structures which may be affected. (iii) The action of carcinogens on susceptible nuclear component. (iiia) The dual dysfunction theory for uni-nucleotide events (1). (iiib) The tether drop theory for chromosomal aberration-like lesions (2). (iiic) The impaired polymerase complex theory for the focal replicative infidelity lesions (3).