Radiation-induced bystander effects, carcinogenesis and models.

Implications for carcinogenesis of radiation-induced bystander effects are both mechanistic and practical. They include induction of second cancers, perturbations to tissue social control and induction of genomic instability and delayed or immediate mutations in areas not receiving a direct deposition of energy. Bystander effects have consequences for DNA damage-mutation-cancer initiation paradigms of radiation carcinogenesis that provide the mechanistic justification for low-dose risk estimates. If carcinogenesis does not result from directly induced DNA mutations, then the carcinogenic initiation process may not simply relate to radiation dose. Modification of the preclonal state through genetic and epigenetic mechanisms may occur. To deal with the complexity of these interactions, a 'chaotic' or 'bifurcation' model invoking autopoietic theory is proposed that could accommodate both beneficial (hormetic) and harmful effects of radiation at comparable doses. Carcinogenesis may then be thought of as the result of a disturbance of the genetic/epigenetic balance occurring within the organ. Ultimate clonality may reflect domination due to selection processes rather than the initiating damage.