Transgenerational Effects in Mice Exposed to Continuous Low-Dose-Rate Gamma-Rays– Analysis of Germ Cell Mutation –Keiji OGURA, Katuyoshi FUJIKAWA, Satoshi TANAKA, Ignacia TANAKA,
Kazuaki ICHINOHE, Yoichi OGISO, Kimio TANAKA
Department of Radiobiology
Abstract
Transgenerational effects of continuous low-dose-rate (LDR) gamma-ray irradiation of male mice havenot been well studied. To clarify incidence of copy number aberrations (CNAs) on the progeny of mice
exposed to radiation, progeny of male C57BL/6J mice continuously exposed to LDR (20 mGy/22 h/day)
gamma-rays for 400 days (total dose: 8000 mGy) was analyzed. Using oligo-microarray CGH (AgilentTechnologies), we have, so far, analyzed a total of 229 genomes (66 progenies from 12 pairs of parents inLDR-irradiated group and 103 progenies from 18 pairs of parents in non-irradiated group). The results
indicate that progeny from LDR-irradiated mice had significantly higher frequencies of genomic aberrations
than progeny from non-irradiated mice (1.06 loci/genome vs. 0.19 loci/genome).

The nucleotide sequenceswere determined at three loci (1.4 kb, 1.5 kb and 135kb deletion) from the LDR-irradiated mice group.
The nucleotide sequences suggest that the 1.4 kb and 1.5 kb deletions were formed by single strand
annealing (SSA) repair, and the 135 kb deletion was formed by non-homologous end-joining (NHEJ) repair.

Table 1 Results of the genomic aberrations analysis using the oligo-microarray CGH
No. ofanalyzed
F1 miceNo. of micewithaberrations

No. oflociaberrating

No. of micewith multipleaberrations

20 mGy/22h/day
irradiated group66

21(32%)

85(Ave. 1.29 loci/generation)

4 (6%)

Non irradiatedgroup103

15(15%)

19(Ave. 0.18 loci/generation)

0 (0%)

P =0.03

P <0.001

1. Mutation frequency in the 20 mGy/22h/day irradiated group is significantly higher than the non-irradiated group.
2. Multiple aberrations were found only in the 20 mGy/22h/day irradiated group.
3. Increase in copy number aberrations (CNAs) were less frequent than decreases.

Table 2 De novo genomic aberrations found in F1 mice
20 mGy/22h/day irradiated group
PF1Copy

Probe IDChrStart

Non-irradiated groupsize

P

F1

Copy

Probe ID

ChrStart

size

大きな変異（103匹中）Large aberrations

大きな変異（66匹中）Largeaberrations
A1

d

A_67_P06933980

9 113994878

133572G

2d

A_67_P04226288

1114741818

72062

E

1

d

A_67_P01942010

957473630

234921

H

5d

A_67_P00568664

2177113983

688713E

5i

A_67_P05889421

648005970

305969H

5d

A_67_P07597258

1241196414

146136G2d

A_67_P08093213

1441807207

3286

K

4

d

A_67_P04816742

35533449

34160

I

5d

A_67_P02200316

1098677432

744874K

5d

A_67_P07881467

1355020816

25412

L2dA_67_P08087383

1438727785

23540

L

4d

A_67_P01456795

6 138658494

32881

Ei

A_53_P142487

8125951601

1535

L

5d

A_67_P07898663

1363501120

1908639F

4
5

A_67_P06477612

837019826

68

L

8

d

A_67_P05018303

3 105191509

132898G

2id

A_67_P04434755

213957250

346

G

5i

A_67_P06783170

949529393

412

B

3

d

A_67_P05197589433730804

94H

1

dA_67_P06382618

7142916412

98

B

5dA_67_P02151317

1068882829

1040

H

1

dA_67_P06671121

8125525315

594
89

小さな変異（66匹中）
Smallaberrations

小さな変異（103匹中）
Small aberrations

B

5d

A_67_P07398579

1174609783

175

I

3

d

A_67_P02693109

1353303865

E

3

d

A_67_P00341736

234273487

100

L

6

d

A_67_P07000727

1022555501

86

G

5

d

A_67_P04083311

144861301

948

N

5A_67_P04221500

1111527682

66A_67_P04007022

17313469

153A_67_P00830676

422048320

230

G

7dA_67_P05313129

489899132

1878

O

7G7dA_67_P04259545

1 131185842

617

P

3iidI

4d

A_67_P02060678

108393959

460

P

3d

A_67_P06620732

8105555233

93J

4d

A_67_P06860168

981442835

327

P

7i

A_67_P03082883

1581575653

71

Q

2

d

A_67_P08008520

13117033940

66

J

4

d

A_67_P00912069

481088876

122L

4dA_67_P05080618

3 133586473

428

A

2d35 loci<1.5 kbF5d15 loci<1.6 kb

H6d10 loci<0.6 kb

L

1d5 loci<0.5 kb

数多くの変異（66匹中）Multiple aberrations

Mice with two de novo genomic aberrations are marked in red. Type ofaberrations is indicated as d (deletion) or i (increase). Multiple aberrations(more than five aberrations in one mouse) are shown in the lower left side.