ABS1hACT Continuous cell lines that secrete both insulin and somatostatin were established by two cooprating groups of investigators from a serially transplantable, radiation-induced, rat islet cell tumor. The cell lines, named RIN-r and RIN-m, were initiated from tumors maintained in inbred rats or in athymic nude mice, respectively. The cultured cells are ppithelioid, free of fibroblast.contamination, and can be cloned.They have a hypodiploid chromosome number, are tumorigenic, and possess amine-handling properties, including high evels of L-dopa decarboxylase and formaldehyde-induced fluorescence. Preliminary analysis of clones revealed a spectrum of insulin secretion from undetectable to relatively high. These clonal cell lines provide important systems to study the biology of insulin and somatostatin. MATERIALS AND METHODS Origin of the cultures. Cultures were initiated from a transplantable islet cell tumor (6) induced by high-dose x-irradiation in an inbred NEDH (New England Deaconess Hospital) rat. The tumor was maintained by serial transplantation in NEDH rats. After nine transplants, it was successfully heterotransplanted into athymic nude mice, BALB/c background (ARS/Sprague-Dawley, Madison, WI). Continuous cell lines were derived either from rat transplants (Joslin group) or from nude mouse heterotransplants (NCI-VA group). These cell lines were named RIN-r and RIN-m, respectively.Establishment of RIN-r Cell Line. Tumors were removed aseptically from recipient rats and cut into small fragments The tumor cells were separated from the connective tissue stroma by washing the fragments with tissue culture medium 199 containing 0.1% fetal bovine serum, 16.5 mM glucose, and 400 units of penicillin per ml. The culture medium used throughout the remainder of the procedure was similar, but contained 10% fetal bovine serum. Erythrocytes present in the original cell suspension were removed by centrifugation (750 X g, 10 min) on a discontinuous gradient consisting of a solution of 25% di-

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We compared and contrasted intracranial (i.c.) and subcutaneous (s.c.) heterotransplantation of small-cell carcinoma of the lung (SCCL) into athymic nude mice. Fresh human SCCL tumor specimens, tumor colonies grown in soft agarose and continuous cell lines were used. Tumors induced by the three types of specimens were similar, but s.c. and i.c. transplants differed. S.c. tumors had longer latent times, were non-invasive and non-lethal. I.c. tumors has shorter latent periods, invariably grew in the meninges, frequently invaded and destroyed the underlying brain, and were lethal. The tumor-inducing dose for i.c. transplantation was 10 to 1,000 times lower than for s.c. transplantation. Pooled colonies of SCCL tumor specimens grown in soft agarose were inoculated i.c. While they contained relatively small numbers of cells (400-10,000), 83% of these colony specimens induced tumors after 58-243 days, confirming the "stem-cell" origin of the colonies. I.c. and s.c. transplants retained the characteristic morphology of SCCL, and, with one exception, did not metastasize to distant organs. Continuous cell lines could be established readily from both types of transplants, and they retained the characteristic cytology, growth and biochemical properties of the original SCCL tumors. I.c. heterotransplantation of SCCL is a useful tool, especially when small numbers of tumor cells are available, and may provide a model to study the biology and therapy of meningeal carcinomatosis.

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