RERF Report No. 16-15

Paper published in Radiation Research§“Metabolic profile as a potential modifier of long-term radiation effects on peripheral
lymphocyte subsets in atomicbomb survivors”
Kengo Yoshida, Eiji Nakashima, Seishi Kyoizumi, Masayuki Hakoda, Tomonori Hayashi, Ayumi
Hida, Waka Ohishi, Yoichiro Kusunoki
Radiat Res 2016 (September); 186(3): 275-82(doi: 10.1667/RR14336.1)
Study Findings
This study revealed that the percentage of naïve CD4 T cells (a subset of CD4 T cells that has not
yet encountered antigens and is known to decrease with age) among peripheral lymphocytes wasinversely associated with radiation dose; and that naïve CD4 T-cell percentages were also inversely
associated with obesity-related indicators such as body mass index (BMI). Furthermore, analyses that
adjusted for high-density lipoprotein (HDL) cholesterol levels found a positive association between
radiation dose and NK-cell percentages.
Explanation
This study examined the association between the percentage of peripheral lymphocyte subsets (Tcells, B cells, NK cells, etc.) and radiation dose as well as obesity-related indicators, among theparticipants of the Adult Health Study (AHS) conducted by the Radiation Effects ResearchFoundation.
1. Study Purpose
Radiation dose-related changes in the composition and function of peripheral lymphocytes arestill today observed in atomic bomb survivors, and changes in metabolic profiles,* including
cholesterol levels, are also suggested. With the understanding in recent years of a strong association
between obesity and the composition and function of peripheral lymphocytes, this study tested thehypothesis that the long-term effects of radiation on lymphocyte subsets may be modified byobesity-related metabolic profiles.
*Metabolic profile: In this study, an aggregation of various biomarkers related to obesity andmetabolic diseases.

2. Study Methods
Counts of peripheral lymphocyte subsets among 3,113 atomic bomb survivors who participated in
AHS health examinations in Hiroshima and Nagasaki during the period from 2000 through 2002 weremeasured using flow cytometry; linear regression analysis was then conducted to determine statisticalassociations of subset percentages in the entire lymphocyte population with radiation dose, as well aswith metabolic profile indicators (BMI, serum total cholesterol, HDL cholesterol, CRP,* HbA1c levels,and prevalence of diabetes mellitus and fatty liver).
*CRP: C-reactive protein, which is induced by inflammation and detected even in mild inflammatory
responses related to obesity.

3. Study Results(1) Association between metabolic profile indicators and lymphocyte subsets
Indicators related to obesity and related diseases, including high BMI and low HDL cholesterollevels, were positively associated with TH1- and B-cell percentages, and inversely associated withnaïve CD4 T-cell and NK-cell percentages. TH1 is a helper T-cell subset involved in inflammatory
response.
(2) Association between radiation exposure and lymphocyte subsets
As in previous studies, a negative association between radiation dose and naïve CD4 T-cellRERF Report No. 16-15

percentages was observed. Furthermore, regression analysis with adjustment for such metabolic
profile indicators as HDL cholesterol levels showed that NK-cell percentages increased with anincrease of radiation dose. A positive association between NK-cell percentages and aging was also
detected. In AHS participants exposed to relatively lower doses, e.g., less than 0.5 Gy, however, we
did not observe a statistically significant association between radiation exposure and these lymphocyte
subsets.
(3) Interaction between radiation exposure and metabolic profiles
Interaction between radiation dose and CRP levels had negative effects on B-cell percentages,
suggesting that a combination of exposure to higher radiation doses and enhanced inflammation may
lead to a decrease in B-cell percentages.
Study SignificanceThe study results suggest that radiation exposure and obesity may both exacerbate one of thecharacteristics of the immunosenescence of T-cells: decrease in naïve CD4 T-cell percentages andincrease in TH1-cell percentages. Furthermore, radiation exposure and subsequent changes inmetabolic profiles, a portion of which might be affected by radiation exposure, may bring about
long-term changes in the composition of lymphocyte subsets. However, it is necessary to verify theassociations observed among radiation exposure, lymphocyte subsets, and metabolic profiles, as wellas the relationships between observed changes and disease development, by conducting future studies,including longitudinal studies based on observations and measurements carried out at multiple points
in time.

The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in Hiroshima
and Nagasaki for around 70 years. RERF’s research achievements are considered the principal scientific basis forradiation 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 ofphysics, chemistry, biology, and medicine. (Impact factor in 2015: 2.67)