Chromosome aberration Chromosome aberration analysis in peripheral analysis in peripheral

lymphocytes of Gulf and lymphocytes of Gulf and Balkans war veteransBalkans war veterans

H.Schröder, A.Heimers, R.Frentzel-Beyme, A.Schott and W.Hoffmann

Radiation Protection Dosimetry, 103:211-219 (2003)

Human T-lymphocyte metaphaseHuman T-lymphocyte metaphase

Karyotype 46, XY

Chromosome- type aberrations Chromosome- type aberrations distinguishable cytologically at mitosisdistinguishable cytologically at mitosis

Two normal chromosomesdicentric chromosome and acentric fragment

centric ring chromosome and acentric fragment

Aberrant metaphaseAberrant metaphase

Metaphase with two dicentric chromosomes and two acentric fragments

Exclusion criteriaExclusion criteria

•Previous radiotherapy and/or medical use of cytotoxic drugs

•Greater than average exposure to diagnostic medical radiation

•Heavy smokers (more than 20 Cigarettes a day over more than 10 years)

•Previous work in the nuclear industry or other badgemonitored occupation

2nd division metaphase with sister chromatid 2nd division metaphase with sister chromatid exchanges (SCE)exchanges (SCE)

Results of the chromosome aberration analysisResults of the chromosome aberration analysis

1 41 G 1001 4 0,0042 37 G 1002 3 0,0033 44 G 1001 7 0,0074 41 B 1003 2 0,0025 36 G 1001 3 0,0036 42 G 1003 2 0,0027 30 B 1002 2 0,0028 32 G 1000 4 0,0049 57 G 1005 1 0,001

10 38 G 1000 1 0,00111 49 G 1002 2 0,00212 34 G+B 1002 3 0,00313 46 G 999 3 0,00314 31 G 1001 1 0,00115 29 G 1001 1 0,00116 54 G 1001 3 0,00317 41 G 938 0 0,00018 40 G 1007 2 0,00219 32 G 1001 3 0,003

Total 18970 47 0,0025Control 45259 23 0,0005

mean frequency

per cellSubject Age

War of the Gulf, G

Balkans, B

Number of analysed

cells

Number of dicentrics

and centric rings

Result of the chromosome aberration Result of the chromosome aberration analysis after groupinganalysis after grouping

GroupNumber of cells

analysed

Number of dic +

cRMean 95%CI- 95%CI+

Gulf, subjects (N=16)

15963 40 0,0025 0,0018 0,0034

Balkans (N=2)

2005 4 0,0020 0,0005 0,0051

Gulf and Balkans (N=1)

1002 3 0,0030 0,0006 0,0088

Distribution of the observed dicentric chromosomes Distribution of the observed dicentric chromosomes and centric ring chromosomesand centric ring chromosomes

Subject u0 1 2

1 998 2 1 1,497 12,852 999 3 0 0,9983 995 5 1 1,280 6,764 1001 2 0 0,9995 998 3 0 0,9986 1001 2 0 0,9997 1000 2 0 0,9998 997 2 1 1,497 12,859 1004 1 0

10 999 1 011 1000 2 0 0,99912 999 3 0 0,99813 996 3 0 0,99814 1000 1 015 1000 1 016 998 3 0 0,99817 938 0 018 1005 2 0 0,99919 998 3 0 0,998

Total 15985 36 3 1,140 12,71Control 45259 23 0 1,000

Variance/ Mean

Distribution

Very rare findings

• Multicentric ring chromosome in a tetraploid metaphase, most probably consting of 4 chromosomes

• One metaphase with pulverized chromosomal material

Results, summaryResults, summary

• Method of chromosome aberration analysis is both sensitive and specific

• 5-fold elevation of dic and cR compared to the control (2.5 per 1000 M vs 0.5 per 1000 M)

• elevation is highly significant• significant elevation of dic and cR also in 9 of the

19 individual cases• distribution of dic and cR deviates from Poisson• very rare finding of a multi-cR in a tetraploid

metaphase and pvz chromosome material• biological half life of dic is 3.5 years, contradicts

to an acute radiation event

Results of the SCE-AssayResults of the SCE-Assay

1 50 209 0-9 4,18±0,312 50 246 1-10 4,92±0,293 50 223 0-10 4,46±0,364 35 135 1-9 3,86±0,375 47 139 0-9 2,96±0,286 50 246 0-11 4,92±0,358 50 219 0-10 4,38±0,319 50 198 0-9 3,96±0,30

Total 382 1615 0-11 4,23±0,12Control 486 2990 0-24 6,16±0,31

Number of cells

analysedSubject

Number of SCE

Range SCE per cell

SCE per cell mean±SEM