SV40-tumorigenesis in mouse.

Abstract

SV40‐transformed cell lines from 8 kidneys and 2 embryos of inbread CBA mice were grown in vitro and repeatedly tested for oncogenicity in adult syngeneic hosts by subcutaneous inoculation of about 50 × 106 cells. In contrast to spontaneously developing permanent mouse embryo lines, these in vitro lines never induced any progressive tumours. After prolonged cultivation, one of the embryonic lines induced progressively growing tumours in irradiated mice, but not in normal ones. When the tumour was passed in vitro the oncogenic potential increased and after 3 passages, tumours were also obtained in untreated animals. The oncogenic potential was retained by in vitro cultivation and increased to a certain degree by in vivo passages. The oncogenic cell titre increased from a TPD50 of about 107 to 104. Corresponding increase in the oncogenic potential was also obtained when the same implantation procedure was carried out upon a population from a single cell derived from the mixed low oncogenic population and shown to be non‐malignant for normal mice. Attempts to correlate the increase in malignancy to other parameters studied failed except for the demonstration of a higher cloning ability of the malignant population. Tumour tissue contained 3 types of clones, 2 of which were present also in the original population otherwise found non‐malignant for normal mice. Irrespective of the type, 7 of 8 clones from the tumours and none of 5 clones from the latter population produced tumours in normal mice. The oncogenic cell titres of most clones were the same as those found for the mixed population. No virus or subviral infectivity could be recovered from cultures of transformed cells or tumours. All cells were positive both in CF tests and in immunofluorescence tests with sera from tumour‐bearing hamsters. No correlation between the amount of complement‐fixing neoantigen and malignancy was found. Tumour development could be prevented by SV40 immunization, indicating that the increase in oncogenicity was not due to loss of tumour specific transplantation antigens. Simultaneous inoculation of a malignant population and the one grown only in vitro did not support a growth of the latter or prevent a tumour production by the former. Tumour‐bearing, not pretreated mice and most of the irradiated ones with tumours had complement‐fixing antibodies against SV40 neoantigens and immunofluorescent antibodies to the nuclear antigen in their sera. High titres were found in animals carrying tumours for a longer time and low or no titres were recorded in animals which died early due to rapidly growing tumours.