Reexamining the role of tissue inflammation in radiation carcinogenesis: a hypothesis to explain an earlier onset of cancer

Abstract

Purpose

Ionizing radiation is a well-known carcinogen, and epidemiologic efforts have been made to evaluate cancer risks following a radiation exposure. The basic approach has been to estimate increased levels of cancer mortality resulting from exposures to radiation, which is consistent with the somatic mutation theory of cancer. However, the possibility that an irradiation might cause an earlier onset of cancer has also been raised since the earliest days of animal studies. Recently, the mutation induction model has been challenged because it is unable to explain the observed dose-related parallel shift of entire mouse survival curves toward younger ages following an irradiation. This is because if it is assumed that only a fraction of the irradiated individuals are affected, the irradiated population would consist of two subpopulations with different mean lifespans, which makes the overall distribution of individual lifespans broader, and hence the slope of the survival curves shallower. To explain this parallel shift, it is necessary to assume that all individuals of a population are affected. As a result of these observations, possible mechanisms which could account for the parallel shift of mouse survival curves were sought by examining the radiation induction of various types of tissue damage which could facilitate an earlier onset of spontaneously arising cancers.

Conclusion

A proposed mechanism postulates that a radiation exposure leads to tissue inflammation which subsequently stimulates spontaneously arising cancers and allows them to appear earlier than usual. This notion is not unprecedented, and because the background incidence of cancer increases exponentially with an increase in age, a slight shift of the onset age toward younger ages may make it appear as if the risk is increased. In this scenario, a radiation exposure induces DNA damage, cell death, chromosome aberrations etc., which leads to the multi-pathway responses including activation of stromal fibroblasts, macrophages and various inflammatory factors. Such an inflamed microenvironment favors the growth of spontaneously arising tumor cells although currently, the sequential order or relative importance of the individual factors remains to be known.

Keywords:

• Radiation carcinogenesis
• inflammation
• tissue activation

Acknowledgement

The author is grateful to Dr. Leon Kapp for his careful reading of the manuscript and Dr. Asao Noda for his comments.

Disclosure statement

The author reports no conflict of interest involved in this work.

Additional information

Funding

This work was supported by the Radiation Effects Research Foundation (RERF) Research Protocol 1-75. The RERF, Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The views of the authors do not necessarily reflect the views of the US or Japanese government.

Notes on contributors

Nori Nakamura

Nori Nakamura, PhD, is a Radiation Biologist and Geneticist working at the Radiation Effects Research Foundation in Hiroshima, Japan, for more than 35 years. He is also interested in biodosimetry methods which include cytogenetic methods and the electron-spin (paramagnetic)-resonance method used to examine tooth enamel.