A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: approach.
Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrate a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age.
Shuryak
Igor
I
Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA. ishuryak@gmail.com
Hahnfeldt
Philip
P
Hlatky
Lynn
L
Sachs
Rainer K
RK
Brenner
David J
DJ
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000473:pathology; D012306:Risk; D013997:Time Factors; D055815:Young Adult