ANS National
 Meetings/
 Sessions

November 1995

Sohei Kondo

(Kinki Univ-Japan)

1. Wound-Healing Error Model for Radon Carcinogenesis

“INTRODUCTION

                “Epidemiological studies of lung cancer in uranium miners exposed to radon suggest that radon is a tumor promoter.¹ I will refine this notion by applying the wound-healing error model proposed for radiation carcinogenesis in general.”

“DATA AND MODEL

“Data on Uranium Miners in Czechoslovakia

                “Figure 1 shows excess lung cancer deaths in miners as a function of cumulative radon exposure for three groups of workers whose average exposure extended over 14 yr (squares), 9.5 yr (triangles), and 5.6 yr (circles).

                “Figure 2 shows that excess small-cell carcinomas plateaued after 100 working level months (WLM), while excess epidermoid carcinomas increased approximately linearly with radon exposure.

“Wound Healing Error Model for Radiation Carcinogenesis

                “Human cancer is a genetic disease due to accumulation of multiple oncomutations in a single cell. Therefore, it takes a long time for a normal cell to develop into a cancerous cell, which explains the steep rise in the cancer incidence with age. I assume that oncomutations occur spontaneously, whether tissues are irradiated or not, but that cells with oncogenic mutations in a tissue moderately injured by radiation have a selective advantage for clonal expansion because the tissue damage must be repaired by cell growth, which creates the opportunity for clonal expansion. Furthermore, if the tissue damage persists for a long time, spontaneously occurring preneoplastic cells will have an increased probability for acquiring the multiple oncomutations necessary for their progeny to produce a cancerous cell."

“DISCUSSION

“The wound-healing error model, in which chronic, long term wounding after irradiation is more oncogenic than a high cumulative exposure to radon over a short time, can nicely explain the observation that workers who spread their radon exposure over more years had more lung cancers (Fig. I). The unique shape of the dose-response curve for small-cell carcinoma, with a plateau at 100-300 WLM and diminution at 500 WLM (Fig. 2), can be explained by the wound-healing error model as follows. If the target tissue has been heavily irradiated, preneoplastic cells will have no selective advantage because cell growth may not be activated due to impairment of the tissue repair capacity. Therefore, primordial cells that produce small-cell carcinomas may be more radiosensitive than squamous cells that produce epidermoid carcinoma. The last assumption should be studied, although it seems to be the case because small cell carcinomas art considered to be derived from neuroendocrine cells of the bronchial epithelium.

“It is firmly established that the excess frequency of mutations after irradiation increases almost linearly with increasing dose and that its value at equal total exposures remains the same or decreases if exposure rates are decreased. However, uranium miners had increased lung cancer at decreased exposure rates (Fig. 1). Therefore, radon is not an oncomutagen. Mutations are the only known radiation effects that increase approximately linearly with the dose of radiation, without a threshold. Thus, no scientific evidence is available to support a linear no-threshold risk of cancer after exposure to radon. Cancer is not a problem of single cells but of cell society.”

1. R. W. HORNUNG, T. J. MEINHARDT, "Quantitative Risk Assessment of Lung Cancer in U.S. Uranium Miners," Health Phys., 52, 417 (1987).

2. S. KONDO, Health Effects of Low-Level Radiation, Kinki University Press, Osaka, Japan, and Medical Physics Publishing, Madison, Wisconsin (1993).

3. E. KUNZ, J. SEVC, V. PLACEK, J. HORACEK, "Lung Cancer in Man in Relation to Different Time Distribution of Radiation Exposure," Health Phys., 36, 699 (1979).

4. J. SEVC, E. KUNZ, L. TOMASEK, V. PLACEK, J. HORACEK, "Cancer in Man After Exposure to Rn Daughters," Health Phys., 54, 27 (1988).