ANS National
 Meetings/
 Sessions

November 1994

Sohei Kondo

(Kinki University Japan)

3. Atomic Bomb Survivors and the Sigmoidal Response Model

Sohei Kondo (Kinki University Japan)

“INTRODUCTION

               “Epidemiological data on health effects of low-level radiation based on 40-yr follow up studies of 75,000 atomic bomb survivors and 35,000 control people show that there were no measurable risks from low-level radiation in regard to non-cancer diseases, genetic, teratogenic, and carcinogenic effects. However, seemingly sigmoidal responses of bomb radiation- induced cancers, which must have been caused by tumorigenic mutations contradict experimental results that mutations linearly increase with increase in radiation dose. An explanation is proposed for this superficial contradiction.”

“HEALTH EFFECTS OF LOW-LEVEL RADIATION IN BOMB SURVIVORS

                “Deaths from non-cancer diseases: Slight but insignificant decreases in non-cancer deaths in bomb survivors¹ exposed to 6 to 19, 20 to 49, 50 to 99, and 100 to 199 cGy occurred as early as 1950-1955 these seemingly beneficial effects of radiation were greater in men than in women² (Table I).

                “Genetic effects (based on studies of 8,000 to 30,000 children born to parents exposed to average doses of 40 to 60 cCy and 8,000 to 45,000 control children): no significant differences were detected in frequencies of sex ratio, birth defects and stillbirth, growth during childhood, chromosome aneuploidy, chromosome translocations, mutations in blood proteins, and leukemia between children from bomb survivors and control children.

                “Birth defects: Children with small head size, mental retardation, and reduction in IQ scores and school performance were born to pregnant mothers exposed to high doses; there were threshold doses of ~50 and 10 cGy respectively, for severe mental retardation and reduction of IQ scores and school performances.

            “Cancer: The dose-response curves for most cancers seen after exposure to bomb radiation have troughs at the low-dose intervals 1 to 5, 6 to 19, and 20 to 49 cGy (Refs. 3 and 4) (Fig. 1). However, whether low doses of radiation really suppressed cancer incidences in bomb survivors cannot be concluded from Fig. 1 alone because o the large statistical uncertainty at each trough. The pooled numbers of cancer deaths in Hiroshima and Nagasaki are large enough to provide statistically significant datas (Table II); the reduced relative risk for colon cancer in the 10- to 19-cGy range is significant.”

“DISCUSSION

               “Suppression of tumorigenesis by cell death: Early stages of colon tumorigenesis involve point mutation of a ras gene to an activated form6 that provides the affected cell with growth advantage a beneficial mutation.1 When such a tumorigenic mutation has been spontaneously induced in an epithelial cell of the colon, resulting pre-cancerous cells may undergo self-killing-termed apoptosis⁷ -upon exposure to lethal signals produced by low-level irradiation, resulting in extinction of pre-cancerous cells (see Ref. 1 for details). Epitheliai cells of the gut are continuously renewed by progeny of stem cells, and stem cells are very sensitive to apoptosis by radiation as low as 20 cGy (Ref. 8). Similarly, low-level irradiation may stimulate apoptosis of preleukemic cells, an explanation for troughs at low doses in the dose response of leukemia in Fig. 1E.

                “Indirect induction of tumorigenic mutations by radiation: Mutations induced by radiation in linear proportion to the dose without threshold are mostly of deleterious or neutral types. Then, how could tumors be induced after high doses of radiation? Available evidence supports the model that tumorigenic mutations are induced indirectly by radiation as a result of long-term up-regulation of growth activities recruited for healing the chronic injury induced in a target organ by an above-threshold dose of radiation1 However, if the organ is given doses of radiation so high as to impair its healing capacity, the incidence of tumors in it will not increase with increase in the dose,¹ an explanation for the dose response curve given in Fig. 1F.”

1. A. KONDO, Health Effects of low-level Radiation, Medical Physics Publishing, Madison, Wisconsin (1993).

2. Y. SHIMIZU et al., Radiat. Res., 130, 249 (1992).

3. Y. SHIMIZU et al., RERFTR 12-87, Radiation Effects Research Foundation, Hiroshima (1987).

4. P. G. SMITH. R. DOLL, Br. Med. J., 284, 449 (1982).

5. Y. SHIMIZU et al., J. Radiat. Res., 32, Suppl. 2, 54 (1991).

6. E. R. FEARON, B. VOCELSTEIN, Cell, 61, 759 (1990).

7. A. H. WYLLIE et al., Int. Rev. Cytol., 68, 251 (1980).

8. C. S. POTTEN, Nature, 269, 518(1977).