The Dose-response Relationships for Tumor Induction after High-LET Radiation.

Abstract

Dose-response relationship/Neutron/Malignant Lymphoma/Myeloid Leukemia/Liver Tumor/Ovarian Tumor This paper presents a review of several studies conducted in our laboratory to examine the carcinogenic effects in mice of high-LET radiation and, for comparison, of low-LET reference radiation. For some specific end-points the following conclusions can be formulated: i) the dose-response curves for myeloid leukemia and malignant lymphoma can be interpreted in terms of induction and inactivation; in particular, the data confirmed that a linear dependence of the induction on dose is adequate to describe the response to fission neutrons, while a pure quadratic dependence is consistent with the experimental data for low-LET radiation; ii) in the liver, a marked age-dependence was demonstrated for radiation-induced tumors with a much higher susceptibility in young than in old mice; also for these tumors the dose-effect curves can be described by a linear and a quadratic relationships for high and low-LET radiation, respectively; iii) data on ovarian tumor induction suggested threshold-like dose responses: these peculiar shapes as well as the absence of a clear radiation quality dependence of the curves are difficult findings to explain using a simple model of radiation action, and they might better be related to a non-stochastic effect of hormonal imbalance following irradiation.

Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

“…Exposure to radiation increases the risk of breast cancer, as revealed by epidemiological studies of atomic bomb survivors and patients who have undergone radiotherapy (1). Neutrons can be used as a type of high linear energy transfer (LET) radiation and produce more complex DNA damage with stronger carcinogenic effects compared to low LET radiation (2). In clinical settings, neutrons are generated as a secondary type of radiation during proton therapy (3), However, the carcinogenic effects of neutrons in humans have not yet been reported.…”

Exome of Radiation-induced Rat Mammary Carcinoma Shows Copy-number Losses and Mutations in Human-relevant Cancer Genes

“…Epidemiological studies on atomic bomb survivors and patients who have undergone radiotherapy have established that ionizing radiation is a risk factor for breast cancer (1). Neutrons are high linear energy transfer (LET) radiation and produce more complex DNA damage, with stronger carcinogenetic effects as compared with low LET radiation, such as γ-rays (2). Thus, there is concern about the breast cancer risk from neutron exposure caused by nuclear accidents and as a secondary radiation during proton therapy, which is increasingly used in the clinical setting (3)(4)(5).…”

Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part II: Hematopoietic system, lung and liver

“…For example, one study using (C57BL/Cne x C3H/HeCne) F1 (BC3F1) and CBA/Cne mice exposed to X-rays at 1.26 to 1.34 Gy/min showed that X-irradiation with 3 Gy or more significantly increased an incidence of hepatoma, but exposure to 7 Gy gave the incidence lower than that of the control value [ 106 ]. The same group also investigated the hepatoma incidence in BC3F1 mice exposed to 40 mGy - 2.56 Gy of X-rays at 60 mGy/min and 680 mGy/min for lower and higher doses, respectively, and they did not find clear dose-dependent hepatoma induction at lower doses, while the incidence of overall solid cancers showed dose-dependent increase [ 107 , 108 ]. A similar conclusion was obtained in the study using (C57BL/6NCrj x C3H/HeNCrj) F1 (B6C3F1) mice exposed to X-rays with 0.5 and 5.0 Gy exposed at 100 mGy/min [ 109 ].…”