Radiation-Induced carcinogenesis: Mechanistically based differences between Gamma-Rays and neutrons, and interactions with DMBA

Igor Shuryak, David J. Brenner, Robert L. Ullrich

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Different types of ionizing radiation produce different dependences of cancer risk on radiation dose/dose rate. Sparsely ionizing radiation (e.g. γ-rays) generally produces linear or upwardly curving dose responses at low doses, and the risk decreases when the dose rate is reduced (direct dose rate effect). Densely ionizing radiation (e.g. neutrons) often produces downwardly curving dose responses, where the risk initially grows with dose, but eventually stabilizes or decreases. When the dose rate is reduced, the risk increases (inverse dose rate effect). These qualitative differences suggest qualitative differences in carcinogenesis mechanisms. We hypothesize that the dominant mechanism for induction of many solid cancers by sparsely ionizing radiation is initiation of stem cells to a pre-malignant state, but for densely ionizing radiation the dominant mechanism is radiation-bystander-effect mediated promotion of already pre-malignant cell clone growth. Here we present a mathematical model based on these assumptions and test it using data on the incidence of dysplastic growths and tumors in the mammary glands of mice exposed to high or low dose rates of γ-rays and neutrons, either with or without pre-treatment with the chemical carcinogen 7,12-dimethylbenz-alpha-anthracene (DMBA). The model provides a mechanistic and quantitative explanation which is consistent with the data and may provide useful insight into human carcinogenesis.

Original languageEnglish (US)
Article numbere28559
JournalPLoS One
Volume6
Issue number12
DOIs
StatePublished - Dec 14 2011

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Gamma Rays
Ionizing radiation
Neutrons
Ionizing Radiation
Gamma rays
carcinogenesis
gamma radiation
Carcinogenesis
Radiation
ionizing radiation
Dosimetry
dosage
Clone cells
Bystander Effect
Neoplasms
Radiation effects
Radiation Effects
Human Mammary Glands
Growth
Stem cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Radiation-Induced carcinogenesis : Mechanistically based differences between Gamma-Rays and neutrons, and interactions with DMBA. / Shuryak, Igor; Brenner, David J.; Ullrich, Robert L.

In: PLoS One, Vol. 6, No. 12, e28559, 14.12.2011.

Research output: Contribution to journalArticle

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