Reference SummaryIshii-Ohba H, Mutat Res 2007 Jun 1;619(1-2):124-33

Title	Existence of a threshold-like dose for gamma-ray induction of thymic lymphomas and no susceptibility to radiation-induced solid tumors in SCID mice.
Authors	Ishii-Ohba H; Kobayashi S; Nishimura M; Shimada Y; Tsuji H; Sado T; Ogiu T
Journal	Mutat Res
Volume	619
Issue	1-2
Year	2007
Pages	124-33
Abstract	Severe combined immune deficiency (SCID) mice exhibit limited repair of DNA double-strand breaks and are sensitive to ionizing radiation due to a mutation of the DNA-dependent protein kinase catalytic subunit gene. To elucidate the effects of deficient DNA double-strand break repair on radiation-induced carcinogenesis, the dose-response relationship for the induction of all tumor types was examined in wild-type and SCID mice. In wild-type mice, the incidence of thymic lymphomas at gamma-ray doses up to 1Gy was almost equal to the background level, increased gradually above 1Gy, and reached a maximum of 12.5% at 5Gy, which is indicative of a threshold dose of less than 1Gy. SCID mice were extremely susceptible to the induction of spontaneous and radiation-induced thymic lymphomas. The incidence of thymic lymphomas in SCID mice irradiated with 0.1Gy or less was similar to the background level; that is, it increased markedly from 31.7% at 0.1Gy to 51.4% at 0.25Gy, and reached a maximum of 80.6% at 2Gy, suggesting the presence of a threshold-like dose at low gamma-ray doses, even in radiosensitive SCID mice. As the average latency for the induction of thymic lymphomas at 0.1Gy was significantly shortened, the effect of 0.1Gy gamma-rays on thymic lymphoma induction was marginal. The high susceptibility of SCID mice to develop thymic lymphomas indicates that thymic lymphomas are induced by a defect in DNA double-strand break repair or V(D)J recombination. Excessive development of tumors other than thymic and nonthymic lymphomas was not observed in SCID mice. Furthermore, our data suggest that the defective double-strand break repair in SCID mice is not a major determinant for the induction of nonlymphoid tumors.
Links	J:120953 – MGI References 17397880 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C.B-17;ICR	Adrenal gland adenocarcinoma		Adrenal gland	12
C.B-17;ICR	Adrenal gland adenocarcinoma	gamma-radiation	Adrenal gland	10 - 15
C.B-17;ICR-Prkdc^scid	Adrenal gland adenocarcinoma		Adrenal gland	12.15
C.B-17;ICR-Prkdc^scid	Adrenal gland adenocarcinoma	gamma-radiation	Adrenal gland	0 - 0.95
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland adenocarcinoma		Adrenal gland	9.43
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland adenocarcinoma	gamma-radiation	Adrenal gland	6.54 - 14.42
C.B-17;ICR	Adrenal gland adenoma		Adrenal gland	32
C.B-17;ICR	Adrenal gland adenoma	gamma-radiation	Adrenal gland	27 - 29
C.B-17;ICR-Prkdc^scid	Adrenal gland adenoma		Adrenal gland	16.82
C.B-17;ICR-Prkdc^scid	Adrenal gland adenoma	gamma-radiation	Adrenal gland	0.8 - 8.57
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland adenoma		Adrenal gland	27.36
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland adenoma	gamma-radiation	Adrenal gland	16.82 - 28.97
C.B-17;ICR	Adrenal gland tumor		Adrenal gland	1 - 41
C.B-17;ICR	Adrenal gland tumor	gamma-radiation	Adrenal gland	2 - 42
C.B-17;ICR-Prkdc^scid	Adrenal gland tumor		Adrenal gland	2.8 - 27.10
C.B-17;ICR-Prkdc^scid	Adrenal gland tumor	gamma-radiation	Adrenal gland	0 - 8.57
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland tumor		Adrenal gland	0 - 36.79
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Adrenal gland tumor	gamma-radiation	Adrenal gland	0.96 - 40.19
C.B-17;ICR	Kidney tumor		Kidney	0
C.B-17;ICR	Kidney tumor	gamma-radiation	Kidney	1 - 6
C.B-17;ICR-Prkdc^scid	Kidney tumor		Kidney	0.93
C.B-17;ICR-Prkdc^scid	Kidney tumor	gamma-radiation	Kidney	0 - 1.9
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Kidney tumor		Kidney	0.94
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Kidney tumor	gamma-radiation	Kidney	0 - 2.88
C.B-17;ICR	Leukocyte leukemia		Leukocyte	5
C.B-17;ICR	Leukocyte leukemia	gamma-radiation	Leukocyte	0 - 3
C.B-17;ICR-Prkdc^scid	Leukocyte leukemia		Leukocyte	5.61
C.B-17;ICR-Prkdc^scid	Leukocyte leukemia	gamma-radiation	Leukocyte	0.93 - 0.95
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte leukemia		Leukocyte	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte leukemia	gamma-radiation	Leukocyte	0.96 - 1.87
C.B-17;ICR	Leukocyte lymphoma	gamma-radiation	Thymus	0.99 - 12.5
C.B-17;ICR	Leukocyte lymphoma		Thymus	1
C.B-17;ICR-Prkdc^scid	Leukocyte lymphoma		Thymus	35.51
C.B-17;ICR-Prkdc^scid	Leukocyte lymphoma	gamma-radiation	Thymus	31.74 - 80.56
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte lymphoma	gamma-radiation	Thymus	0 - 3.74
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte lymphoma		Thymus	4.72
C.B-17;ICR	Leukocyte lymphoma		Leukocyte	62
C.B-17;ICR	Leukocyte lymphoma	gamma-radiation	Leukocyte	46 - 51
C.B-17;ICR-Prkdc^scid	Leukocyte lymphoma		Leukocyte	22.43
C.B-17;ICR-Prkdc^scid	Leukocyte lymphoma	gamma-radiation	Leukocyte	12.96 - 75.24
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte lymphoma		Leukocyte	64.15
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte lymphoma	gamma-radiation	Leukocyte	50.47 - 54.21
C.B-17;ICR-Prkdc^scid	Leukocyte tumor	gamma-radiation	Leukocyte	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Leukocyte tumor	gamma-radiation	Leukocyte	0
C.B-17;ICR	Liver hepatocellular adenoma		Liver	0
C.B-17;ICR	Liver hepatocellular adenoma	gamma-radiation	Liver	9 - 24
C.B-17;ICR-Prkdc^scid	Liver hepatocellular adenoma		Liver	6.54
C.B-17;ICR-Prkdc^scid	Liver hepatocellular adenoma	gamma-radiation	Liver	0.93 - 4.76
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver hepatocellular adenoma		Liver	2.83
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver hepatocellular adenoma	gamma-radiation	Liver	5.61 - 17.76
C.B-17;ICR	Liver hepatocellular carcinoma		Liver	3
C.B-17;ICR	Liver hepatocellular carcinoma	gamma-radiation	Liver	8 - 21
C.B-17;ICR-Prkdc^scid	Liver hepatocellular carcinoma		Liver	8.41
C.B-17;ICR-Prkdc^scid	Liver hepatocellular carcinoma	gamma-radiation	Liver	0 - 6.67
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver hepatocellular carcinoma		Liver	2.83
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver hepatocellular carcinoma	gamma-radiation	Liver	13.08 - 26.92
C.B-17;ICR	Liver tumor		Liver	3 - 6
C.B-17;ICR	Liver tumor	gamma-radiation	Liver	4 - 41
C.B-17;ICR-Prkdc^scid	Liver tumor		Liver	0 - 14.02
C.B-17;ICR-Prkdc^scid	Liver tumor	gamma-radiation	Liver	0 - 10.48
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver tumor		Liver	5.66 - 8.49
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Liver tumor	gamma-radiation	Liver	2.88 - 36.54
C.B-17;ICR	Lung adenocarcinoma		Lung	31
C.B-17;ICR	Lung adenocarcinoma	gamma-radiation	Lung	26 - 30
C.B-17;ICR-Prkdc^scid	Lung adenocarcinoma		Lung	16.82
C.B-17;ICR-Prkdc^scid	Lung adenocarcinoma	gamma-radiation	Lung	0 - 5.71
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung adenocarcinoma		Lung	16.04
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung adenocarcinoma	gamma-radiation	Lung	15.89 - 25
C.B-17;ICR	Lung adenoma		Lung	21
C.B-17;ICR	Lung adenoma	gamma-radiation	Lung	20 - 23
C.B-17;ICR-Prkdc^scid	Lung adenoma		Lung	17.76
C.B-17;ICR-Prkdc^scid	Lung adenoma	gamma-radiation	Lung	0 - 3.81
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung adenoma		Lung	20.75
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung adenoma	gamma-radiation	Lung	10.28 - 20.56
C.B-17;ICR	Lung tumor		Lung	4 - 42
C.B-17;ICR	Lung tumor	gamma-radiation	Lung	0 - 43
C.B-17;ICR-Prkdc^scid	Lung tumor		Lung	1.87 - 29.91
C.B-17;ICR-Prkdc^scid	Lung tumor	gamma-radiation	Lung	0 - 9.52
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung tumor		Lung	1.89 - 34.91
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Lung tumor	gamma-radiation	Lung	0 - 34.58
C.B-17;ICR	Mammary gland adenocarcinoma		Mammary gland	10
C.B-17;ICR	Mammary gland adenocarcinoma	gamma-radiation	Mammary gland	3 - 20
C.B-17;ICR-Prkdc^scid	Mammary gland adenocarcinoma		Mammary gland	6.54
C.B-17;ICR-Prkdc^scid	Mammary gland adenocarcinoma	gamma-radiation	Mammary gland	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland adenocarcinoma		Mammary gland	11.32
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland adenocarcinoma	gamma-radiation	Mammary gland	5.61 - 16.82
C.B-17;ICR	Mammary gland adenoma		Mammary gland	1
C.B-17;ICR	Mammary gland adenoma	gamma-radiation	Mammary gland	1 - 3
C.B-17;ICR-Prkdc^scid	Mammary gland adenoma		Mammary gland	0
C.B-17;ICR-Prkdc^scid	Mammary gland adenoma	gamma-radiation	Mammary gland	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland adenoma		Mammary gland	2.83
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland adenoma	gamma-radiation	Mammary gland	0.93 - 0.96
C.B-17;ICR	Mammary gland tumor		Mammary gland	2 - 10
C.B-17;ICR	Mammary gland tumor	gamma-radiation	Mammary gland	0 - 25
C.B-17;ICR-Prkdc^scid	Mammary gland tumor		Mammary gland	0 - 6.54
C.B-17;ICR-Prkdc^scid	Mammary gland tumor	gamma-radiation	Mammary gland	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland tumor		Mammary gland	4.72 - 12.26
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Mammary gland tumor	gamma-radiation	Mammary gland	0.93 - 26.17
C.B-17;ICR	Ovary - Granulosa cell tumor		Ovary - Granulosa cell	4
C.B-17;ICR	Ovary - Granulosa cell tumor	gamma-radiation	Ovary - Granulosa cell	41 - 49
C.B-17;ICR-Prkdc^scid	Ovary - Granulosa cell tumor		Ovary - Granulosa cell	3.74
C.B-17;ICR-Prkdc^scid	Ovary - Granulosa cell tumor	gamma-radiation	Ovary - Granulosa cell	0 - 11.43
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary - Granulosa cell tumor		Ovary - Granulosa cell	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary - Granulosa cell tumor	gamma-radiation	Ovary - Granulosa cell	28.04 - 44.86
C.B-17;ICR	Ovary adenocarcinoma		Ovary	0
C.B-17;ICR	Ovary adenocarcinoma	gamma-radiation	Ovary	1 - 5
C.B-17;ICR-Prkdc^scid	Ovary adenocarcinoma		Ovary	0.93
C.B-17;ICR-Prkdc^scid	Ovary adenocarcinoma	gamma-radiation	Ovary	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary adenocarcinoma		Ovary	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary adenocarcinoma	gamma-radiation	Ovary	1.87 - 4.81
C.B-17;ICR	Ovary adenoma		Ovary	2
C.B-17;ICR	Ovary adenoma	gamma-radiation	Ovary	10 - 14
C.B-17;ICR-Prkdc^scid	Ovary adenoma		Ovary	0
C.B-17;ICR-Prkdc^scid	Ovary adenoma	gamma-radiation	Ovary	0 - 2.86
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary adenoma		Ovary	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary adenoma	gamma-radiation	Ovary	7 - 15.38
C.B-17;ICR	Ovary tumor		Ovary	4 - 9
C.B-17;ICR	Ovary tumor	gamma-radiation	Ovary	5 - 60
C.B-17;ICR-Prkdc^scid	Ovary tumor		Ovary	1.87 - 5.61
C.B-17;ICR-Prkdc^scid	Ovary tumor	gamma-radiation	Ovary	0 - 13.33
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary tumor		Ovary	0.94
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Ovary tumor	gamma-radiation	Ovary	9.35 - 64.42
C.B-17;ICR	Skin tumor		Skin	7
C.B-17;ICR	Skin tumor	gamma-radiation	Skin	2 - 5
C.B-17;ICR-Prkdc^scid	Skin tumor		Skin	0.93
C.B-17;ICR-Prkdc^scid	Skin tumor	gamma-radiation	Skin	0 - 2.78
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Skin tumor		Skin	1.89
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Skin tumor	gamma-radiation	Skin	2.88 - 3.74
C.B-17;ICR	Spleen tumor		Spleen	7
C.B-17;ICR	Spleen tumor	gamma-radiation	Spleen	2 - 8
C.B-17;ICR-Prkdc^scid	Spleen tumor		Spleen	0.93
C.B-17;ICR-Prkdc^scid	Spleen tumor	gamma-radiation	Spleen	0 - 0.95
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Spleen tumor		Spleen	7.55
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Spleen tumor	gamma-radiation	Spleen	7 - 11.21
C.B-17;ICR	Uterus adenocarcinoma		Uterus	5
C.B-17;ICR	Uterus adenocarcinoma	gamma-radiation	Uterus	1 - 3
C.B-17;ICR-Prkdc^scid	Uterus adenocarcinoma		Uterus	5.61
C.B-17;ICR-Prkdc^scid	Uterus adenocarcinoma	gamma-radiation	Uterus	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus adenocarcinoma		Uterus	0
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus adenocarcinoma	gamma-radiation	Uterus	0 - 2.88
C.B-17;ICR	Uterus adenoma		Uterus	8
C.B-17;ICR	Uterus adenoma	gamma-radiation	Uterus	6 - 7
C.B-17;ICR-Prkdc^scid	Uterus adenoma		Uterus	8.41
C.B-17;ICR-Prkdc^scid	Uterus adenoma	gamma-radiation	Uterus	0 - 0.8
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus adenoma		Uterus	5.66
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus adenoma	gamma-radiation	Uterus	2.8 - 3.85
C.B-17;ICR	Uterus polyp		Uterus	29
C.B-17;ICR	Uterus polyp	gamma-radiation	Uterus	7 - 8
C.B-17;ICR-Prkdc^scid	Uterus polyp		Uterus	43.93
C.B-17;ICR-Prkdc^scid	Uterus polyp	gamma-radiation	Uterus	0 - 3.81
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus polyp		Uterus	15.09
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus polyp	gamma-radiation	Uterus	3.74 - 7.48
C.B-17;ICR	Uterus tumor		Uterus	9 - 46
C.B-17;ICR	Uterus tumor	gamma-radiation	Uterus	4 - 20
C.B-17;ICR-Prkdc^scid	Uterus tumor		Uterus	3.74 - 56.07
C.B-17;ICR-Prkdc^scid	Uterus tumor	gamma-radiation	Uterus	00 - 3.81
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus tumor		Uterus	11.32 - 30.19
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	Uterus tumor	gamma-radiation	Uterus	3.74 - 14.95
C.B-17;ICR	(Unspecified organ) tumor	gamma-radiation	(Unspecified organ)	4 - 98.02
C.B-17;ICR	(Unspecified organ) tumor		(Unspecified organ)	17 - 95.00
C.B-17;ICR-Prkdc^scid	(Unspecified organ) tumor		(Unspecified organ)	17.76 - 91.59
C.B-17;ICR-Prkdc^scid	(Unspecified organ) tumor	gamma-radiation	(Unspecified organ)	3.81 - 99.11
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	(Unspecified organ) tumor		(Unspecified organ)	19.81 - 97.17
(C.B-17;ICR-Prkdc^scid x C.B-17;ICR)F1-Prkdc^scid/+	(Unspecified organ) tumor	gamma-radiation	(Unspecified organ)	13.08 - 97.12

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