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.
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 1 Gy was almost equal to the background level, increased gradually above 1 Gy, and reached a maximum of 12.5% at 5 Gy, which is indicative of a threshold dose of less than 1 Gy. 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 0.1 Gy or less was similar to the background level; that is, it increased markedly from 31.7% at 0.1 Gy to 51.4% at 0.25 Gy, and reached a maximum of 80.6% at 2 Gy, 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 0.1 Gy was significantly shortened, the effect of 0.1 Gy 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.
authors.affiliation: Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. ishii_h@nirs.go.jp <ishii_h@nirs.go.jp>
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ishii-Ohba
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsuji
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sado
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ogiu
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics; D013953:Thymus Neoplasms / Q000209:etiology* / Q000235:genetics