The suitability of immunosuppressed mice kept in a standard animal unit as recipients of human tumour xenografts

Hay, Joanne; Morten, John; Clarke, Barbara Jean; Swinton, June

doi:10.1258/002367785780942561

“…Female CBA mice of around six weeks of age were rendered incompetent immunologically by thymectomy followed by whole-body radiation and treatment with cytosine arabinoside by a modification of the method of Steel et al (1978) (Hay et al, 1985). CHL, 208F, and the derivative myc and ras expressing lines were suspended in Dulbecco's PBS at a concentration of 1-2x 108 ml-1, and inoculated subcutaneously in volumes of 0.1 ml, either to the left groin or the mid-dorsal region around 4 weeks after whole body irradiation.…”

Section: Animalsmentioning

confidence: 99%

Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression

Wyllie

¹

,

Rose²,

Morris³

et al. 1987

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Summary The effects of expression of human c-myc and both mutated (T24) and normal forms of human Ha-ras-1 were studied in an aneuploid rat fibroblast line (208F). Mutated T24 Ha-ras was also studied in a near-diploid cell derived from early passage Chinese hamster lung fibroblasts (CHL). In contrast to the parental fibroblasts, cells expressing any of the human oncogenes engendered rapidly growing tumours in immune-suppressed animals. Blood-and lymph-borne metastases were observed from both ras-and mycexpressing cells. In general ras-expressing cells were more aggressive than those expressing myc. In the 208F background, expression of c-myc was associated with an incidence of mitosis similar to that in tumours expressing T24 Ha-ras, but incidence of single cell death by apoptosis was higher. Quantitatively, expression of human oncogene mRNA was constant during growth in vivo, and similar to that sometimes observed in human neoplasms. Of 9 endogenous proto-oncogenes, 7 showed no change in expression from the parental fibroblasts, but c-abl and c-fos were strongly expressed in all cells expressing human ras or myc. Thus these tumorigenic cells, although transfected with single human oncogenes, all expressed oncogenes with both nuclear-and membrane-associated products.

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“…23 On balance we have found thymectomised irradiated mice cheaper and easier to use than nude animals. 24 The time taken for xenografts to grow to an adequate size for testing makes the use of this system for predicting the drug sensitivity of individual tumours in the clinical setting impractical. As a model 15…”

Section: Resultsmentioning

confidence: 99%

Human tumour xenografts growing in immunodeficient mice: A useful model for assessing chemotherapeutic agents in bronchial carcinoma

1987

Lung Cancer

0

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Xenografts from eight human bronchial carcinomas have been established in CBA/Lac mice rendered immunodeficient by neonatal thymectomy followed three weeks later by whole body irradiation (7.35 Gy (735 rads)) after a priming dose of cytosine arabinoside. Growth rates of individual tumour lines remain constant and the histological and chromosomal characteristics of the original tumour are maintained through multiple serial passages over many months. With specific growth delay as the principal end point this system may be used to assess the response of histologically different lung tumours to chemotherapeutic agents.Chemotherapy is now widely used for palliation in most patients with small cell lung tumours' and in minority of those with inoperable non-small cell malignancies.2 The great variation in the response of individuals to the currently used drugs and the need to develop more effective agents, particularly for non-small cell tumours, has led to much interest in methods of assessing the efficiency of anticancer treatments in the laboratory.3 The success of in vitro testing of bacterial sensitivities to antibiotics led early workers to attempt to evaluate the effects of anticancer drugs on malignant cells growing in tissue culture and to correlate the results with the clinical response seen in the patient.4 " The results were disappointing,3 although the development of newer clonogenic assays appeared more encouraging.67Various animal models have been used in the development and testing of new anticancer agents. Transplantable rodent tumours, such as the Lewis lung carcinoma, have proved of little value as appreciable differences in sensitivity between these and human tumours were found. In an attempt to overcome this problem many workers have grown human tumours either in congenitally athymic "nude" mice89 or in rodents rendered immunodeficient by various techniques.'°" We have used such a system and find it a useful animal model for assessing the activity of anticancer agents in bronchial carcinoma.

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“…o Since, however, Controls human tumours grow mice, Controls most experiments can be completed in about 10 weeks from transplantation, and the period that an animal remains adequately immunosuppressed can be TreQted extended to over six months when high doses of irradiation are used.22 The use of nude mice may help to overcome this difficulty but these animals are costly, require elaborate husbandry, and are also capable of mounting a host response.23 On balance we have found thymectomised irradiated mice cheaper and easier to use than nude animals. 24 The time taken for xenografts to grow to an adequate size for testing makes the use of this system for predicting the drug sensitivity of individual tumours in the clinical setting impractical. As a model 15 20 for assessing new anticancer agents in bronchial carcinoma, however, it is inexpensive and easy to establish while, as Shorthouse and colleagues have wvs) on xenograft shown,18 19 …”

Section: Resultsmentioning

confidence: 99%

Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma.

Fergusson¹,

Carmichael²,

Smyth³

1986

Thorax

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Xenografts from eight human bronchial carcinomas have been established in CBA/Lac mice rendered immunodeficient by neonatal thymectomy followed three weeks later by whole body irradiation (7.35 Gy (735 rads)) after a priming dose of cytosine arabinoside. Growth rates of individual tumour lines remain constant and the histological and chromosomal characteristics of the original tumour are maintained through multiple serial passages over many months. With specific growth delay as the principal end point this system may be used to assess the response of histologically different lung tumours to chemotherapeutic agents.Chemotherapy is now widely used for palliation in most patients with small cell lung tumours' and in minority of those with inoperable non-small cell malignancies.2 The great variation in the response of individuals to the currently used drugs and the need to develop more effective agents, particularly for non-small cell tumours, has led to much interest in methods of assessing the efficiency of anticancer treatments in the laboratory.3 The success of in vitro testing of bacterial sensitivities to antibiotics led early workers to attempt to evaluate the effects of anticancer drugs on malignant cells growing in tissue culture and to correlate the results with the clinical response seen in the patient.4 " The results were disappointing,3 although the development of newer clonogenic assays appeared more encouraging.67Various animal models have been used in the development and testing of new anticancer agents. Transplantable rodent tumours, such as the Lewis lung carcinoma, have proved of little value as appreciable differences in sensitivity between these and human tumours were found. In an attempt to overcome this problem many workers have grown human tumours either in congenitally athymic "nude" mice89 or in rodents rendered immunodeficient by various techniques.'°" We have used such a system and find it a useful animal model for assessing the activity of anticancer agents in bronchial carcinoma.

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The suitability of immunosuppressed mice kept in a standard animal unit as recipients of human tumour xenografts

Cited by 10 publications

References 3 publications

Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression

Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression

Human tumour xenografts growing in immunodeficient mice: A useful model for assessing chemotherapeutic agents in bronchial carcinoma

Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma.

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