Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection

Draft document: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection
Submitted by Nori Nakamura, RERF
Commenting as an individual

1) Fetal exposyre and cancer risk:
We have recently published a paper that showed that rat fetuses DID record radiation damage (ie translocations) in mammary tissues when examined as adults, and the translocation frequencies were nearly the same as those in the exposed mothers (Nakano M, Nishimura M, et al. Fetal irradiation of rats induces persistent translocations in mammary epithelial cells similar to the level after adult irradiation, but not in hematolymphoid cells. Radiat Res. 2014 Feb;181(2):172-6. doi: 10.1667/RR13446.1. Epub 2014 Feb 10.).
As mentioned in the paper, SD rats are susceptible to radiation-induced mammary cancers whist fetal irradiation does not induce mammary cancers.
Thus, the reason why fetuses are refractory to carcinogenic effect of radiation is not simply a loss of damaged stem cells during post-natal development at least in the rat mammary system.

The related parts are indicated below: 
page 11, lines 410~
page 66 (section 120~122)

2) My naive question on the relative risk
On page 49 (section 74), mutation theory of cancer is indicated. I am wondering if we assume that a spontaneous cancer occurs as a result of 5 independent mutations and irradiarion allowed skipping any one of the 5 steps, it is expected that the maximum relative risk should not be more than 5/4 or 1.2. Of course, the observed fact does not fit the expectation. Where is the problem? I think this is because earlir onset age is not taken into account. I am a bit afraid that the draft is missing this viewpoint.  

3) page 67, section (124, line 2765); The sentense that "The ERR of radiogenic cancer is inversely related to the age at exposure for many cancer types, ie high for the young age with an age-dependent dfecline of the risk (Preston et al 2007)" may look misleading because it is also true that for many types of cancer (ex, breast cancer risk), ERR at age 70 is the same regardless of the age at exposure. In these cases, exposure at young age is at high risk only because they are associated with young onset risk, whiuch never occurs for those who were exposed at older ages.