@misc{oai:repo.qst.go.jp:00070318,
 author = {Shimada, Yoshiya and Nishimura, Mayumi and Imaoka, Tatsuhiko and Kakinuma, Shizuko and Takabatake, Takashi and Shang, Yi and Amasaki, Yoshiko and Hirano, Shinobu and Yamada, Yutaka and Takeda, Shino and 島田 義也 and 西村 まゆみ and 今岡 達彦 and 柿沼 志津子 and 高畠 貴志 and 尚 奕 and 甘崎 佳子 and 坂入 しのぶ and 山田 裕 and 武田 志乃},
 month = {Nov},
 note = {Given both the established vulnerability of children to ionizing radiation and a progressive increase in the use of medical radiation, understanding the relationship between children's health outcome and radiation exposure is critical for our children's wellbeing.  These conditions have forced the radiation-regulatory bodies to draft global initiatives on radiation protection for children.  In order to obtain the parameters of radiation protection for children, we have studied the effect of gamma-rays, X-rays, neutrons and heavy ions on cancer induction and lifespan shortening of fetuses and children.  Final goals of this research group are to propose age-weighting factors and relative biological effectiveness (RBE) of neutrons and heavy ions for fetuses and children for radiation protection.
(1) Lifespan shortening
Female and male B6C3F1 mice, which have been used in a wide variety of toxicological studies, were exposed to gamma rays (137Cs), carbon ions (energy, 290 MeV/u; LET, 13 keV/um) and neutrons (energy, 2 MeV) at various ages during fetal to mature adulthood periods.  The ages examined were pre-implantation, major organogenesis, late fetal, neonatal, prepubertal, post-pubertal and mature adult stages.  Male mice at the neonatal stage were more sensitive than those at the adult stage.  Surprisingly, irradiation at the late fetal stage had little influence on lifespan shortening for both genders. Irradiation with carbon ions at the adult stage shortened the lifespan to a similar extent as that with gamma-rays, suggesting a small RBE of carbon ions.  Carbon ions were more potent, however, in reducing lifespan than gamma rays when fetal and neonatal mice were exposed.   
(2) Cancer induction
     Radiation risks are dependent upon both tissue types and the age at exposure.  Breast is one of the most susceptible organs to radiation-associated cancer risk. The data suggest that gamma irradiation at prepubertal stage at 1 Gy resulted in the highest incidence of mammary carcinomas than other stages.  On the other hand, the dose-effect relationship of lung tumors did not change much depending on the age at irradiation.   
    The age effect on tumor development of kidney, brain (medulloblastoma), intestine, and lymphoid organ (thymus) was examined using mutant and genetically engineered animals of human cancer models.   Peri-natal and infant stages were the most sensitive to the development of tumors of kidney and brain in Eker rats and Ptch1+/- mice, respectively.  Brain tumors developed in a dose-dependent fashion with considerable effects even at a low dose of 100 mGy. We found intra-chromosomal deletions at Ptch1 locus in radiation-induced tumors, which was not observed in spontaneous tumors. This molecular change enabled us to identify the radiation-induced tumors even at a low dose as low as 50 mGy.  Irradiation at the infant stage induced more intestinal tumors in ApcMin/+ mice than that at the adult stage, and the second hit event was, again, intra-chromosomal deletions.  The incidence of T-cell lymphomas was the highest in Mlh1-/- mice exposed at infant stage, but the late fetal mice were unexpectedly resistant. In the lymphomas from Mlh1-/- mice, the frequent frame shift mutations at mononucleotide repeat sequences in Ikaros were observed. 
(3) Uranium
   Health effects for children in depleted uranium-polluted areas and uranium mining areas are of recent concerns.  Uranium and its compounds have the potential to cause nephrotoxicity.  We found that elimination of uranium was delayed in neonates than adults, and that rapidly growing S3 segments during infant period re-accumulated the uranium, thereby resulting in persistent apoptotic figures observed.    
\n  In conclusion, peri- and post-natal ages are the most susceptible for radiation carcinogenesis., NIRS-Workshop as an IAEA Collaborating Centre},
 title = {Radiation exposure at early stage of life},
 year = {2010}
}