(chromosome inversions, durlications, translocations, deletions, etc.) and remain viable. However, although only a very small fraction of alpha interactions give rise to-viable mutated cells, these survive to preliferate, whereas cells which suffer lethal changes are elininated from the cell population. Thus in the case of long-tern exposure of tissue to internal alpha emitters at low dose rates there is a cumulative ‘increase in the population of cells which have survived one or more chromosome structural changes. However it is equally obvious that a cell whose nucleus is subjected to repeated alpha interactions within the mean life of the cell hes only a negligible chance of survival. It is likely that the production of a radiation-induced tumor begins with the formation of a single malignant cell characterized by a combina tion of two or more chromosome changes and/or gene mutations. The alpha radiation-induced bone tumor incidence in dogs is observed to be proportional to the square of the alpha dose (13) implying that a sequence of two or more low probability events must be involved. This is consistent with the two-mutation and nultiple-nutation theories of cancer on the age distribution of cancer in man. (20,21) based On the basis of these consider- ations the production of a pilignant cell involves a sequence of events, as follows: (3) production of a viable mutated cell; (2) clone growth from the mutated cell; (3) production of a second viable mutation in one or more of the clone; »(4) growth of a clone of doubly-mutated cells; etc. Thus, for a two-mutation sequence, the tumor risk would be proportional to the Re? (t/t), where R is the alpha dose rate, t is the time of exposure, and T is the mean life of the normal cell and singly mutated cell, The term (t/t.) represents the influence of the growth of the clone of the singly-mutated cell on the long-term risk. This tumor risk relationship makes it abundantly clear that a linear a saree Oe CER Be Tat . Vy ame ky coe ot aS Tee t pare SO ay t ae fie oe oe Wee Bo Seu RE gn "y