Comparison of dose-dependent enhancing effects of ?-ray irradiation on urethan-induced lung tumorigenesis in athymic nude (nu/nu) mice and euthymic (nu/+) littermates

Abstract

The role of immunological surveillance in carcinogenesis is still controversial. In our previous experiments, urethan-induced lung tumorigenesis in athymic (nu/nu) mice and euthymic (nu/+) littermates was examined, and it was concluded that immunosurveillance mediated by T cells could not be demonstrated. However, the reported enhancement of development of various tumors following ionizing radiation might be achieved through modulating the host immunological conditions. In the present experiment, nu/nu and littermate nu/+ mice were treated with 1-4 Gy gamma-rays alone at 6 weeks of age or treated with urethan at 0.5 mg/g body weight when aged 14 days followed by 1-4 GY gamma-rays 4 weeks later. Lung tumors were assessed at 6.5 months of age. Ionizing radiation itself caused a very low incidence of these lesions. On the other hand, multiplicities and incidences of lung tumors after urethan treatment at 0.5 mg/g body weight were similar between the two phenotypically different groups of mice (1.66 and 1.84 tumors/mouse, 73% and 80% incidences, for nu/nu and nu/+ cases respectively). This urethan-induced lung tumorigenesis was significantly enhanced by gamma-rays in both nu/nu and nu/+ mice, and the magnitude of tumor enhancement was somewhat higher in nu/+ mice than in nu/nu mice, especially with a 2-Gy dose. In conclusion, it may be said that lung tumorigenicity of gamma-ray irradiation itself and the enhancing effect of radiation on urethan-induced tumorigenesis are scarcely influenced by immunosurveillance mechanisms mediated by T cells.

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

“…It has been shown that g-radiation at low dose (2-4 Gy) promoted tumor cell infiltration with no pronounced impact on host immune function in nude mice (54). The ALDH high subpopulation accounted for 1.89% AE 0.85% of the total PC3M cells that initiated metastatic growth in the bone marrow of the irradiated immune-suppressive host mice, whereas unsorted PC3M cells homed to the bone marrow only when tumor cells were implanted by intracardiac injection.…”

“…Athymic NMRI nude male mice ages 8 to 12 weeks (Taconic Europe) were used. For intravenous injection of tumor cells, mice were sublethally irradiated with two doses of 2 Gy administered 2 hours apart using a 137 Cs source at a dose rate of 1 Gy/minutes as described (54). Equal amounts of ALDH …”

The role of natural killer cells in pulmonary immunosurveillance

“…Since the thymus is involved in the development of the majority of T cells (61, 62), these studies suggest that T cells do not significantly contribute to tumor immunosurveillance in the lung. Furthermore, nu/nu and nu/+ mice responded similarly to ionizing radiation treatment of urethane-induced lung cancer (64). …”