° 6 Ct. target afforded by the cell chromosomes. " ir This follows necessarily from the fact that most alpha interactions with ceil chromosomes lead to the (17,18) subsequent mitotic death of the cell, as Barendsen has shown The production of a malignant cell calls for a sequence of two or more low probability events and thus cannot be speeded up by the application of . massive alpha doses, but rather only by subjecting a much larger number of cells to a limited number of interactions. Additionally, assuming that the tumor risk to the tissue subjected to alpha irradiation is proportional to Re (e/TDs expiained above, it is apparent that the- alpha activity concentration or the activity per particle which is eauated to a given tumor risk decreases with increasing time of exposure and also that 4 given risk can be attributed to smaller cumulative doses when the time of exposure t ir appreciably longer than the mean life of the cell, To. Brues ‘27? and Burch (28) both pointed out that the two-mutation theories of carcinosepesis (20,21) would imply an exceptionally high effectiveness of widely spaced radiation for tumor production. It is proposed that just such a ‘dose rate relationship serves to reconcile the observed significant tumor risk in cigarette smokers with the presence of a persistent lung burden of insoluble smoke particles: involving a total of only a few picocurirs of 2120p, (14) | 3. ? 2 “Hot” Pud,, Particle Risks: If the above tentative conclusions are correct, then the same considerations must apply in the assessment of tumor risks for hot particles. In this connection a preliminary considera- tion of the influence of specific alpha activity and particle size of the hot - alpha emitting particles is in order. 1 Raabe et al. 62%) report an apparent rate of dissolution of ***Pu0, dn lung fluid which is two orders of magnitude higher than that observed for ***Pud, particles. Such a dramatic difference in the chemical behavior