- Comments: 3- This is true and should be noted for future reference. It should also be noted that this dose-incidence relationship indicates not only an increase in tumor incidence with increasing dose size and dose rate (associated with dose size), but also an increase in tumorigenic. effectiveness per unit dose with increasing dose size and dose rate. This kind of dose-incidence relationship shows decreasing effectiveness of doses in the rising portion of the dose-incidence curve with the decreasing dose rate that is associated with decreasing dose. Page 4, lines 16-18 - "This is consistent with the two-mutation and multiple-mutation theories of cancer (20,21) based on the age distribution of cancer in man." Comments: This is also consistent with the multistage theories of mechanisms of carcinogenesis requiring cellular initisting events (malignant cell transformation) plus promotional events such as local tissue damage or damage of structure and function of more remote but relevant organs or systems by one or a combination of agents or conditions. Page 4, lines 18-27 - "On the basis of these considerations the production of a malignant cell involves a sequence of events, as follows: (1) 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 R°t?(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." ~ Comments: The author states that, r for a two-mutation sequence, the tumor risk would be proportional to Rr? (t/Te), where R is alpha dose rate, t is time of exposure, T, is mean Life of normal cell and singly mutated cell, and the term (t/T,) represents the influence of the growth of the clone of the singly-mutated cell on the long-term risk.