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Observations on the chromosomes of cells from 5 human malignant tumors are reported. Each tumor had one or more distinctive marker chromosomes. Marker chromosomes were present in a total of 700 of 711 metaphases from these tumors, which included an early malignant lesion of the cervix showing minimal invasion. Two tumors (a Stage 4 carcinoma of the cervix and a reticulum cell sarcoma, both untreated) yielded preparations of high quality. The 7 best-spread metaphases from the former with the modal number of chromosomes (60) had identical karyotypes, as did 16 from the latter with the modal number of 49. Less extensive data on 13 other tumors, 8 of which had marker chromosomes, are also presented. The data presented here, together with the published data on the chromosomes of cells from human tumors, support the view that human malignant tumors frequently but not invariably arise from a single cell in which chromosome changes have occurred. A carcinoma of the corpus uteri, to which brief reference is made, is a possible exception: Most metaphases had apparently normal karyotypes. The role of chromosome abnormalities (particularly structural changes) in the malignant transformation is discussed. Possible parallels between the chromosome findings in the cells of malignant tumors and those in chronic myeloid leukemia are considered. It is suggested that in tumors there may be both specific changes (perhaps involving chromosomes structurally changed) and coincidental changes. Variation in the coincidental changes might largely account for the wide differences between the karyotypes of different tumors.

Certain responses of mouse and hamster cells to polyoma virus were examined with respect to their specificity as "indicators" of neoplastic conversion in vitro. These responses included the development of transplantation antigens and changes in morphologic growth pattern, cytology, karyology, rates of proliferation, and glycolytic activities. Under limited conditions, i.e., in short-term, slow-growing cultures, the morphologic change in growth pattern and increases in glycolytic activity and proliferation rate induced by polyoma virus appeared to correlate with neoplastic conversion. However, in long-term or rapidly growing short-term cultures, similar morphologic patterns occurred in cells that subsequently tested as non-neoplastic. Also, such patterns could be induced by polyoma virus in cells already neoplastic. Cells that had undergone "spontaneous" neoplastic conversion frequently showed none of these morphologic features of virus-transformed cells. Prolonged culture of cells without added virus resulted in increased glycolytic activities and proliferation rates equivalent to those of virus-transformed cells. These changes occurred in at least one cell line long before evidence of neoplastic conversion. The cytologic changes in the virus-treated neoplastic cells were similar to those usually associated with neoplastic cells in vivo and may possibly serve as sensitive indicators of in vitro neoplastic conversion. From the observations of this study, the change in morphologic growth pattern is interpreted not as loss of "contact inhibition," but as a proliferative response accompanied by decreased adhesion of cells to the glass substrate.

Inbred CBA/H and CBA/H-T6 mice received implants of 15 X 22 mm plastic films. Plastic inserts and tissue capsules were cut in thirds at half monthly and monthly intervals. The first portion of the inserts and capsules was left in the original animal. The second portion was separated and individually transplanted into recipients that differed from the original animals with respect to the T6 marker chromosome. The third portion and all tumors which developed in original and recipient animals were examined by karyological, histological, and cultural methods. Film pieces caused tumors in recipient animals up to 9 months after transfer, capsule tissue only up to about 1 month after transfer. Tumors in original and corresponding recipient animals were identical in their chromosomal stemlines and pace of premalignant maturation. The karyotype of the stemline was never discovered among the film-attached cell population because there seemed to be no cell division. This points to the existence of a single, specific premalignant cell clone residing on the film surface in a dormant state of nondivision many months before tumor appearance. At the end, the (pre)malignant cells detached from the film, invaded the capsule tissue, and propagated to produce the tumor within about 4 weeks. The existence of a specific inhibition phenomenon during the premalignant phase is suggested.