RERF Report No. 3-13

Paper published in Radiation Research§“Fetal Irradiation of Rats Induces Persistent Translocations in Mammary EpithelialCells Similar to the Level after Adult Irradiation, but Not in Hematolymphoid Cells”
Mimako Nakano, Mayumi Nishimura, Kanya Hamasaki, Shuji Mishima, Mitsuaki Yoshida, AkifumiNakata, Yoshiya Shimada, Asao Noda, Nori Nakamura, Yoshiaki Kodama
Radiat Res 2014 (February); 181(2):172–6(doi: 10.1667/RR13446.1)

Study Findings
Examination of rat chromosomes following fetal irradiation showed radiation-induced
chromosome aberrations in mammary epithelial cells similar to those found in the mothers, but very
few aberrations were observed in lymphocytes. This result demonstrates the presence of tissue
specificity with regard to chromosome aberrations following fetal radiation exposure.
Explanation
Previous studies on humans and mice have shown that fetal exposure to radiation fails to induce
persistent chromosome aberrations in blood lymphocytes. Such a low level of response to radiation
exposure is counterintuitive in view of the generally accepted belief that fetuses are highly sensitive toradiation. In this study, we examined chromosomes of mammary tissues in rats irradiated in utero todetermine whether or not the same result is observed in other tissues.
1. Objectives
With the aim of determining whether or not the frequencies of chromosome aberration
attributable to fetal radiation exposure differ by tissue type, this study examined mammary epithelial
cells in rats. In addition, chromosomes of spleen lymphocytes were examined in a subgroup of rats tocompare the frequencies of aberration between blood cells and epithelial cells.
2. MethodsPregnant rats were irradiated at a dose of 2 Gy on day 17.5 of gestation. Mammary tissues werecollected from the mothers and their offspring six, nine, and 45 weeks after irradiation. After
mammary epithelial cells were cultured, chromosome samples were prepared by a conventionalmethod. To detect translocations, we adopted the fluorescent in situ hybridization (FISH) technique tostain chromosomes 2 and 4 green and red, respectively (see Figure), and 800 cells were examined foreach rat. The same procedure was followed to examine the chromosomes of cultured spleenlymphocytes.
3. Results(1) The mean translocation frequency in mammary epithelial cells of rats irradiated in utero with adose of 2 Gy was 3.7% (n = 23). This figure is similar to the mean frequency of 2.9% observed in
the mothers (n = 5).
(2) The translocation frequency in spleen lymphocytes was 0.0–0.6% among rats irradiated in utero(mean frequency: 0.4%, n = 13), which was significantly lower than the mean translocation
frequency of 3.5% observed in the mothers (n = 3).
(3) Translocation frequencies were similar at six, nine, and 45 weeks after irradiation.
As noted above, this study showed that the frequency of chromosome aberrations in themammary cells of rats irradiated in utero, and examined at six to 45 weeks of age, was as high as thatin the mothers. In contrast, the translocation frequency in lymphocytes was high in the mothers but
considerably lower among rats irradiated in utero (about 10% of that of the mothers), supporting thefindings in previous studies on mice and humans. These results suggest tissue specificity in thechromosome aberration pattern in fetal exposure. If the translocation frequency is assumed to be anindex of the carcinogenic effect of radiation, this study suggests that fetal radiation exposure may
induce persistent carcinogenic damage in mammary stem cells and progenitor cells. However, the1RERF Report No. 3-13

results of another report showed that fetal exposure in rats did not increase breast cancer risk. No clear
reason has been identified that can explain this discrepancy, highlighting the need for further study.

Figure. Detection of translocation (t) by FISH. Chromosomes 2 and 4 are stained green and red,respectively, and the remaining chromosomes are stained blue. Chromosomes stained in twocolors (indicated by arrows) are detected as abnormal chromosomes (translocations).

The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in Hiroshima
and Nagasaki for more than 60 years. RERF’s research achievements are considered the principal scientific basis
for radiation risk assessment by the United Nations Scientific Committee on the Effects of Atomic Radiation(UNSCEAR) and for recommendations regarding radiation protection standards by the International
Commission on Radiological Protection (ICRP). RERF expresses its profound gratitude to the A-bomb survivors
and survivors’ offspring for their cooperation in our studies.
§Radiation Research, which is an official monthly journal of the Radiation Research Society, publishes original,
peer-reviewed papers and review articles on radiation effects and related issues in the fields of physics,
chemistry, biology, and medicine. (Impact factor in 2012: 2.698)

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