We characterized two human cell lines (Hs578T and Hs578Bst), which provide several unique features that should be useful in the study of breast disease. Hs578T, derived from a carcinosarcoma, is epithelial in origin. Hs578Bst, established from normal tissue peripheral to the tumor, is myoepithelial in origin. This is the first report of companion cell lines, one malignant and one normal, established from the same organ.

Nine epithelial cell strains were established from normal mouse liver, mammary gland, ovary, and ear skin. After overnight digestion by collagenase in growth medium, intact glandular fragments produced many islands of epithelial outgrowth when plated in an enriched medium. Contaminating fibroblasts were removed by selective trypsinization. These strains continue to show morphologic and ultrastructural features typical of epithelial cells after 10-50 subcultures. In addition, several strains continue to form secretory vesicles, or hemicysts, on confluent cell sheets. All but 1 strain have maintained a majority population of diploid cells, but all strains show increasing numbers of near-triploid cells. Five strains produced tumors (benign cystadenomas, adenocarcinomas, and sarcomas) when inoculated into isogeneic mice. Type-C oncornaviruses were seen in all but 2

Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal.

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The ability of unmanipulated, antilymphocyte serum (ALS)-treated, and X-irradiated nude BALB/c female mice (in their 13th backcross generation) to serve as hosts for 10 human lymphoblastoid cell lines as well as for peripheral blood lymphocytes from healthy humans was compared. The 10 lymphoma lines included 7 previously characterized and reported in the literature. Significant differences with respect to both latency period for tumor appearance and success rate for tumor transplantation were detected among the 3 experimental groups. The unmanipulated mice were poor recipients for lymphoma heterotranplants, and tumors were produced in only two instances. In contrast, 6 tumor lines were successfully transplanted in mice inoculated with ALS, and all 10 lines were successfully transplanted in X-irradiated recipients. Although tumors were readily produced in ALS-treated and X-irradiated mice, no gross or histologic evidence of focal or distant metastases was apparent. Human lymphoblastoid cells were recultured, essentially unchanged, from the heterotransplants from 6 of 7 tumors tested. Although the tumor line HT 1460, originally from a human lymphoma, was successfully transplanted in all 3 groups, only mouse cells were recultured. The use of X-irradiation, rather than ALS, to immunosuppress nude mice offers a more standardized method for heterotransplanting human tumor cell lines and permits ready comparisons between laboratories. Furthermore X-radiation permits transplantation and subsequent study of lymphoblastoid tumors that are otherwise difficult to successfully transplant in nude mice.