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Science 26 September 1958:
Vol. 128. no. 3326, pp. 693 - 699
DOI: 10.1126/science.128.3326.693
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Articles

Critique of the Linear Theory of Carcinogenesis

Present data on human leukemogenesis by radiation indicate that a nonlinear relation is more probable

Austin M. Brues 1

1 Director of the Division of Biological and Medical Research, Argonne National Laboratory, Lemont, Illinois.

1) Present data on human leukemogenesis by radiation fail to indicate a linear relation between dose and effect. Because data are scanty, such a hypothesis cannot be ruled out statistically, but it is less probable than a nonlinear or threshold relation.

2) Other instances in which carcinogenic agents have been examined from the standpoint of dose and dose-rate relations show many clear instances where the relation is nonlinear and none in which linearity is unquestionably demonstrated.

3) Theoretical consideration of the probability that a single critical molecular event, such as a mutation, will give rise to cancer indicate that a malignant change must be an extraordinarily improbable result of such a perturbation. It is also very difficult to reconcile this mechanism with the rather comparable spontaneous and induced-cancer incidences in species with greatly different numbers of cells.

4) Any scheme in which multiple events caused by the carcinogen are required to produce a tumor is incompatible with a linear relation, while, if a disordered state of tissue is an important factor, a true threshold may even occur. There is much evidence, from cancer research of all sorts, indicating that one or both of these conditions is involved in the carcinogenic process.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Edward B. Lewis, 1918-2004.
J. F. Crow and W. Bender (2004)
Genetics 168, 1773-1783
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Radiation Carcinogenesis: The Sequence of Events.
L. J. Cole and P. C. Nowell (1965)
Science 150, 1782-1786
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Irradiation Leukemogenesis.
J. S. Lawrence (1964)
JAMA 190, 1049-1054
   Abstract »    PDF »
Life Shortening and Tumor Production by Strontium-90.
V. E. Archer and B. E. Carroll (1960)
Science 131, 1808-1809
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Strontium-90 in Man III: The annual increase of this isotope and its pattern of world-wide distribution in man are defined.
J. L. Kulp, A. R. Schulert, and E. J. Hodges (1959)
Science 129, 1249-1255
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