Inderscience Publishers

A new approach to individual prognostication of cancer development under conditions of chronic radiation exposure

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This paper describes a new approach to modelling carcinogenesis, including that induced by ionising radiation. The specific feature of the developed approach is that the model, still adhering to the mutational theory of carcinogenesis, includes parameters of intracellular processes which can be measured for any individual. The assumptions laying the basis for this approach are that cell malignisation results from inefficient functioning of a number of barrier mechanisms on the cell's way from the primary DNA damage to phenotypically manifested mutation/aberration initiating or promoting carcinogenesis, and inefficient functioning of the barrier mechanisms is caused, in turn, by one or several genetic and/or epigenetic events, the number and type of which are of no importance for this approach. The paper points out the necessity and possibility to include model parameters that reflect the status of such intercellular mechanisms as the system of antioxidant protection, repair and apoptosis. The theoretical formalism of the model structure is presented as the generalisation of the concepts of multiple-stage and multiple-pathway models for describing the new biological approach to modelling. Also, the paper discusses issues such as schemes for measuring the parameters included in the model, approaches to individual risk estimation and further generalisation of the model.

Keywords: carcinogenesis, individual modelling, chronic exposure, cellular barrier mechanisms, apoptosis, repair, antioxidant system, multiple-stage models, low radiation, radiation exposure, cancer development, ionising radiation

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