Atomic Bomb Survivors [II]

Chromosome aberration analysis 1983-1985      (METEX Collaboration Study)

This study was performed by a collaborative study funded by MEXT Scientific Research Grant (#58380019 for 1983-1985) on gDose assessment of A-bomb radiation by chromosome aberrationsh. 

Members of collaborative study
     Awa, A. (Rad Effects Res Foundation)

    Abe, S. (Hokkaido University)
    Ejima, Y. (Kyoto University)
    Furuyama, J. (Hyogo Medical College)
    Hayata, I. (National Inst Radiol Sci) 
Hirai, M. (University of Tokyo)
Honada, T. (Rad Effects Res Foundation)

Ichimaru, M. (Nagasaki University)
Ikushima, T. (Kyoto University)

Ishii, Y. (Osaka University)
Ishihara, T. (National Inst of Radiol Sci)
 
Kamada, N. (Hiroshima University)
Kishi, K. (Kyorin University)
Kodama, S. (Kyoto University)
Matsubara, S. (Tokyo Med Dent Univ)
Sadamori, N. (Nagasaki University)
Sasaki, M. S. (Kyoto University) (*Charman)
 
Sofuni, T. (National Inst. Of Health Sci)
Sonta, S. (Aichi Birth Defects Res Inst)
 
Takatsuji, T. (Nagasaki University)
Tatsumi, J. (Nagasaki University)
Tezuka, H. (National Inst Genetics)
Tsuji, H. (National Inst Radiol Sci)
 

Categories in the table:
     Subject ID: Hiroshima (H), Nagasaki (N);     Sex: Male (M), Female (F),     ATB: Age (yrs) at the time of bombing,    Shielding: No shielding (0), Japanese wooden house (2), Concrete building (3), Shaded by concrete building (4)
     Acute symptoms: Burn (B), Diarrhea (D), Fever (F), Epilation (E)

.
No Subject Date of Sex Age Distance Shielding Symptoms No. of Aberrations Cells Distribution of cells with Dic+Ring
ID sampling (ATB) (km) cells Tri Dic Rc Ra aM F del S del X1Cu X2Cu Cs 0 1 2 3 4 5 6
1 ABH03001 1983.09.09 M 26.4 0.57 1 F 1,508 0 16 3 2 39 17 4 4 3 17 5 35 1,491 16 2 1
2 ABH03002 1983.09.09 M 20.0 0.95 1 EDBF 1,664 0 8 1 1 63 14 4 2 2 16 1 57 1,654 10
3 ABH03003 1983.09.12 M 19.6 0.95 0 EDBF 1,531 0 13 1 3 228 14 4 1 1 15 5 194 1,517 12 1 1
4 ABH03004 1983.09.12 F 16.5 0.80 3 - 1,730 0 12 3 0 21 17 4 3 3 17 2 16 1,716 1
5 ABH03005 1983.09.12 F 25.0 1.24 3 - 1,741 0 8 4 3 17 16 5 2 2 19 3 14 1,725 15 1
6 ABN04004 1983.09.22 F 17.0 0.70 4 EDF 1,800 0 11 2 2 20 17 8 5 3 20 5 16 1,786 14
7 ABN04009 1983.09.29 M 18.8 1.50 0 BF 1,700 0 1 0 0 6 5 3 0 0 5 0 5 1,699 1
8 ABN04012 1983.10.06 M 5.9 1.40 1 - 1,700 0 7 0 1 11 5 2 0 0 6 4 11 1,692 8
9 ABN04013 1983.10.06 F 18.9 1.50 1 ED 1,800 0 5 3 0 11 8 3 2 2 10 2 9 1,792 8
10 ABN04014 1983.10.06 M 19.4 1.20 0 EDF 1,800 0 4 1 0 43 6 3 4 3 10 1 38 1,795 5
11 ABH05013 1983.10.21 M 14.5 0.85 0 EDBF 1,975 1 3 1 3 215 11 8 9 8 18 1 187 1,967 7 1
12 ABH05016 1983.11.16 F 25.5 0.80 1 EDBF 1,941 0 16 2 5 65 31 15 4 4 28 2 60 1,922 16 2 1
13 ABN06019 1983.10.13 F 0.9 0.90 0 ED 1,900 1 5 0 1 64 6 2 0 0 3 3 61 1,987 2 1
14 ABN06045 1983.12.08 M 36.1 1.50 0 - 2,000 0 12 3 2 36 21 8 7 6 21 1 33 1,984 15 1
15 ABN06049 1983.12.15 M 16.2 1.40 0 EBF 1,916 0 9 0 0 38 12 7 1 1 12 4 36 1,909 6 1
16 ABN06032 1983.11.17 F 11.9 1.00 1 D 1,200 0 4 3 0 9 8 2 1 1 10 0 9 1,193 7
17 ABH06029 1984.04.18 F 25.9 1.60 1 - 1,525 0 0 1 0 11 2 1 2 2 4 0 11 1,522 1
18 ABH07001 19.85.03.02 M 26.4 0.93 1 EDF 1,250 0 4 0 0 65 9 6 4 4 12 1 61 1,246 4
19 ABH07002 1985.03.02 F 23.1 0.93 1 EDF 1,000 0 0 1 0 41 3 3 1 1 4 1 40 999 1
20 ABN08001 1985.04.10 M 15.8 1.80 1 EDB 1,600 0 5 0 1 9 8 4 2 2 11 1 9 1,594 6
21 ABN08002 1985.04.10 M 20.9 1.20 1 E 1,500 0 0 0 1 8 2 2 0 0 3 0 7 1,499 1
22 ABN08003 1985.04.10 M 29.6 1.40 3 D 1,500 0 0 0 1 7 0 0 0 0 1 0 6 1,499 1
23 ABN08004 1985.04.10 M 25.2 0.69 3 - 1,500 1 1 1 0 21 2 1 1 1 3 1 18 1,498 2
.

Parameters of Bombing  DS02 free-in-air shielded kerma (Gy) for RERF survivor cohorts, modified from glss13morth data of RERF (http://rerf.org.jp)
Hiroshima
          Bomb type: Little boy (Uranium type)
          Bombing: August 6, 1945; 8:15 a.m.
        Burst height: 600}20 m
          Energy yield: 16}2 kt

Nagasaki

        Bomb type: Fat man (Plutonium type)
          Bombing: August 9, 1945; 11:02 a.m.
          Burst height: 503}10 m
        Energy yield: 21}2 kt 
 


Testing for the uniformity of chromosome scoring among scorers

      Currently, the inter-laboratory collaborative studies are often organized for chromosome aberration analysis of the radiation exposed persons, especially for those supposed to be exposed to low-level radiation where large scale data analysis is needed for the dose evaluation, or those involved in radiation accident where there is an immediate need for the biological dose assessment. In such collaborative study, the variability or uniformity of the results obtained by individual scorer is always a matter of important concern. We developed the statistical method for the assessment of  variability of the participants of the collaborative analysis.

(1) Uniformity test for the scoring efficiency in one sample

     Let p2 be the probability to score aberrations in a cell by scorer K, and p1 be the probability to score aberrations in a cell by the rest of scorers, N-1, where N is the total number of scorers. The uniformity of the scoring efficiency is tested by the null hypothesis,

p1=p2

     The number of aberrations, a, in the number of cells scored, n, follow a binomial distribution,

B(a2:n2,p2) for K

B(a1:n1,p1) for N-1.

    The statistical test for p of the two binomial distributions may be possible by assuming that, under the null hypothesis, a2 follows the hypergeometric distribution. That is, with a=a1+a2 and n=n1+n2, the probability density follows the hypergeometric function

p(a2)=p(a2:n2,a,n)=[comb(a; a2)comb(n-a;n2-a2)]/comb(n;n2)

     Then, the lower tail probability of a2 is

LP=sum[i-0 to a2] p(i)

     And the upper tail probability of a2 is

LP=sum[i=a2 to n2] p(i)

2) Uniformity test for the scoring efficiency in multiple samples
    Similarly, for the sample number i (i=1,2,3,c..M), SL as the sum of LP can be obtained, and the probability of SL being below x is expressed by
                                                                                                                        PSL(x)=sum[PL1(a1)+LP2(a2)+ . . . . +LPM(aM)] p1(a1)p2(a2) . . . . . . .pM(aM)

     Similarly, PSU(x) is obtained for the sum of UP being below probability density of x. If the PSL or PSU are below significance level (i.g., 0.005), the scoring of the scorer K is significantly different from that of averaged efficiency of the rest of scorers. If the PSL is blow significance level, the scorer K shows significantly underscore. If the PSU is blow the significance level, the scorer K shows significantly overscore as compared to the average of the rest of scorers.

3) Results and implication for the issue of overdispersion
     The results are summarized in the following Table. In the scoring of unstable chromosome aberrations (dicentrics, rings, fragments) and hence the cells containing those aberrations (X1Cu cells), only three scorers show significant deviation from the group central values. This indicates that the inter-individual (or inter-laboratory) variability in the scoring efficiency is not significantly large.
     In contrast, most of the scorers significantly differ in detecting stable-type aberrations (or Cs cells); they are either over-scoring or under-scoring as compared with the central value of the group. In another word, there is great variability in the frequencies of Cs cells distributed over of central value (over-dispersion). Such inter-individual variability is observed among scorers in the same laboratory.
     The great variability in the scoring efficiency for Cs cells may not be solely due to the slight difference in the scoring criteria of individual scorer. The major reason may stem from the uncertainty of determination that, in the scoring of acquired aberrations, the aberration figures ought to be determined only in one cell that has been selected under the low-power microscopy. To keep unbiased scoring, the cell once selected under low-power microscope should be analyzed anyhow and cannot be rejected unless special reason. Such uncertainty is greater for the conventional Giemsa staining, becomes lesser for G-banding method, and lesser for FISH method.

.
Scorer Probability X1Cu-cells Cs-cells Scorer Probability X1Cu-cells Cs-cells Scorer Probability X1Cu-cells Cs-cells Scorer Probability X1Cu-cells Cs-cells
A upper 54.0 - 6.1 - E upper 81.6 - 100 « I upper 98.9 « 98.7 « M upper 17.4 - 95.4 «
lower 47.0 85.6 lower 27.1 0 lower 0.9 0.3 lower 84.4 1.7
B upper 14.1 - 0 ͺ F upper 1.4 ͺ 3.4 ͺ J upper 42.4 - 99.3 « N upper 88.9 « 99.5 «
lower 89.7 100 lower 98.5 99.3 lower 58.7 2.4 lower 3.0 0.8
C upper 30.1 - 0 ͺ G upper 54.3 - 0 ͺ K upper 94.3 - 99.9 ͺ O upper 84.9 - 2.6 ͺ
lower 71.0 100 lower 50.5 100 lower 11.9 0 lower 31.1 97.5
D upper 8.9 - 96.0 « H upper 85.5 - 99.0 « L upper 25.4 - 0.2 ͺ P upper 83.5 - 90.3 «
lower 88.9 1.7 lower 30.3 0 lower 67.4 100 lower 8.5 3.6
[ͺ]: Sum of upper tail probability is significantly small (over-score)
[«]: Sum of lower probability is significantly small (under-score)
[ - ]: No significant at 5% level.
.