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Irradiated compared with nonirradiated NSG mice for the development of a human B-cell lymphoma model
Deepti Chadalavada1, Trinka W Adamson2, John C Burnett1
1Department of Molecular and Cellular Biology, City of Hope, Beckman Research Institute, Duarte, California, USA.
Abstract:
NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice are a superior strain for the engraftment of human tumors, as they provide an ideal model to explore the potency, toxicity, and dosage of therapeutic drugs. Although whole-body nonlethal irradiation is often performed to enhance engraftment, the need for irradiation to establish a human B-cell lymphoma model using the NSG strain has not been addressed. In the current study, a mouse model of B-cell lymphoma was established by intravenous injection of human B-cell lymphoma Z138 cells into mice with and without irradiation. Tumor development, signs of engraftment, survivability of engrafted mice, histopathology, and immunohistochemistry were evaluated. Potential sex-associated variations in the model were assessed also. Irradiation of NSG mice did not enhance tumor cell engraftment, and nonirradiated animals had increased survivability. Mice with irradiation survived for a median of 27 d before being euthanized due to signs of morbidity, whereas those without irradiation had a median survival of 35 d. Both irradiated and nonirradiated mice were normal in activity until 3 wk after the injection of cells. At that time, the mice started to show signs of lymphoma including ruffled fur, decreased activity, and hindlimb paralysis. There were no significant differences in evaluated parameters between male and female mice. Therefore, we conclude that a model of B-cell lymphoma can successfully be established by using Z138 cells in nonirradiated male and female NSG mice.
Insights
Irradiation is not necessary to enhance human B-cell lymphoma engraftment in NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice. Nonirradiated mice showed improved survival and successful tumor development, establishing a viable model for drug studies.
Area of Science:
- Immunology
- Oncology
- Animal Models
Background:
- NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice are widely used for human tumor xenograft studies.
- Whole-body irradiation is a common method to enhance tumor engraftment in immunodeficient mice.
- The necessity of irradiation for establishing a human B-cell lymphoma model in NSG mice remains uninvestigated.
Purpose of the Study:
- To determine if whole-body irradiation enhances human B-cell lymphoma engraftment in NSG mice.
- To evaluate the impact of irradiation on tumor development, engraftment, and survival in this model.
- To assess potential sex-associated variations in the B-cell lymphoma NSG mouse model.
Main Methods:
- Human B-cell lymphoma Z138 cells were intravenously injected into irradiated and nonirradiated NSG mice.
- Tumor development, engraftment signs, survival rates, histopathology, and immunohistochemistry were assessed.
- Sex-specific differences in model parameters were evaluated.
Main Results:
- Irradiation did not improve tumor cell engraftment in NSG mice.
- Nonirradiated mice exhibited significantly longer median survival (35 days) compared to irradiated mice (27 days).
- Both groups developed lymphoma signs approximately 3 weeks post-injection; no significant sex-based differences were observed.
Conclusions:
- Whole-body irradiation is not required for establishing a human B-cell lymphoma model using Z138 cells in NSG mice.
- Nonirradiated NSG mice provide a viable and more survivable model for human B-cell lymphoma studies.
- This model is suitable for both male and female NSG mice, simplifying experimental design for therapeutic drug evaluation.
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