Preparation of Immunosuppressed Mice

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.67 Various 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. Address for reprint requests: Dr RJ Fergusson, ICRF Medical Oncology Unit, Western General Hospital, Edinburgh EH4 2XU. Accepted 29 October 1985 Methods PREPARATION OF IMMUNOSUPPRESSED MICE Thymectomy was performed by retrosternal aspiration'2 on 3 week old male and female CBA/Lac mice. Three weeks later they underwent whole body x irradiation (7.35 Gy (735 rads) via a 250 KVp, 15 mA source with a Thoraeus Ii filter at 0.37 Gy/min