From Muller to mechanism: How LNT became the default model for cancer risk assessment

Environmental Pollution
Edward J Calabrese

Abstract

This paper summarizes the historical and scientific foundations of the Linear No-Threshold (LNT) cancer risk assessment model. The story of cancer risk assessment is an extraordinary one as it was based on an initial incorrect gene mutation interpretation of Muller, the application of this incorrect assumption in the derivation of the LNT single-hit model, and a series of actions by leading radiation geneticists during the 1946-1956 period, including a National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel (Anonymous, 1956), to sustain the LNT belief via a series of deliberate obfuscations, deceptions and misrepresentations that provided the basis of modern cancer risk assessment policy and practices. The reaffirming of the LNT model by a subsequent and highly influential NAS Biological Effects of Ionizing Radiation (BEIR) I Committee (NAS/NRC, 1972) using mouse data has now been found to be inappropriate based on the discovery of a significant documented error in the historical control group that led to incorrect estimations of risk in the low dose zone. Correction of this error by the original scientists and the application of the adjusted/corrected data back to the BEIR I (NAS/NRC, ...Continue Reading

References

Jan 1, 1978·Perspectives in Biology and Medicine·C Auerbach
Sep 1, 1975·Journal of Toxicology and Environmental Health·D G HoelM A Schneiderman
May 1, 1977·Journal of the National Cancer Institute·R E AlbertE Anderson
Nov 18, 1977·Science·J Cornfield
Nov 1, 1973·Mutation Research·R Voss, R Falk
Jun 1, 1995·Genetics·J F Crow
Jul 14, 1995·Science·G Taubes
Mar 1, 1994·Carcinogenesis·S L NelsonA J Grosovsky
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·L B Russell, W L Russell
Nov 28, 1997·International Journal of Radiation Biology·N Colussi, P H Lohman
Dec 31, 1997·Genetics·J F Crow, S Abrahamson
Aug 27, 1999·Environmental and Molecular Mutagenesis·T NohmiT Sofuni
Feb 11, 2000·Radiation Research·J L SchwartzA W Hsieb
Mar 13, 2003·World Journal of Gastroenterology : WJG·Sheng-Xue LiuYong Liu
Nov 19, 1954·Science·L J STADLER
Dec 19, 1958·Science·W L RUSSELLE M KELLY
Feb 1, 1965·Proceedings of the National Academy of Sciences of the United States of America·B B WEBBER, F J DESERRES
Jan 1, 1951·Cold Spring Harbor Symposia on Quantitative Biology·B McCLINTOCK
Jun 1, 1950·Proceedings of the National Academy of Sciences of the United States of America·B McCLINTOCK
Feb 1, 1927·Proceedings of the National Academy of Sciences of the United States of America·C S Gager, A F Blakeslee
Aug 1, 1926·Proceedings of the National Academy of Sciences of the United States of America·C Stern
Jan 1, 1928·Proceedings of the National Academy of Sciences of the United States of America·L J Stadler
Sep 1, 1928·Proceedings of the National Academy of Sciences of the United States of America·H J Muller
Jul 29, 2006·International Journal of Hygiene and Environmental Health·Wanwisa SudprasertMathuros Ruchirawat
Nov 1, 1953·Genetics·B McClintock
Jun 14, 1929·Science·B McClintock
Jul 22, 1927·Science·H J Muller
Jun 17, 1949·Science·D E Uphoff, C Stern
Mar 10, 2009·Radiation Research·Hideaki ToyokuniMasami Watanabe
Jan 26, 2010·Radiation Research·Naohito OkudairaTetsuya Ono
Mar 9, 1946·Nature·C AUERBACH, J M ROBSON
Jul 26, 2011·Environmental and Molecular Mutagenesis·Edward J Calabrese
Jul 28, 2013·Archives of Toxicology·Edward J Calabrese
Jan 8, 2016·Dose-response : a Publication of International Hormesis Society·Edward J Calabrese

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Citations

Dec 19, 2018·European Journal of Nuclear Medicine and Molecular Imaging·Poul F Høilund-Carlsen
Oct 1, 2020·Dose-response : a Publication of International Hormesis Society·Paul A Oakley, Deed E Harrison
Jun 8, 2018·Philosophy, Ethics, and Humanities in Medicine : PEHM·Edward J Calabrese
Jan 2, 2019·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Shizuyo Sutou
Dec 19, 2018·Journal of Cell Communication and Signaling·Edward J Calabrese
Dec 14, 2018·Dose-response : a Publication of International Hormesis Society·A Alan MoghissiVanessa Vanderdys
Sep 27, 2018·International Journal of Molecular Sciences·Edward J Calabrese
Apr 19, 2019·Journal of Cell Communication and Signaling·Walter J Kozumbo, Edward J Calabrese
May 20, 2020·Dose-response : a Publication of International Hormesis Society·Paul A Oakley, Deed E Harrison
Dec 15, 2019·The Science of the Total Environment·Evgenios Agathokleous, Edward J Calabrese
Jul 7, 2019·Chemico-biological Interactions·Edward J Calabrese, Robert J Golden
Aug 19, 2020·Environmental Research·Edward J Calabrese
Jul 23, 2020·Revista española de medicina nuclear e imagen molecular·J P Suárez Fernández
Jul 23, 2019·Toxicology·Evgenios Agathokleous, Edward J Calabrese
Aug 1, 2021·International Journal of Radiation Biology·Annum DawoodColin Seymour

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