Spontaneous fusion between Ehrlich ascites tumor cells and host cells in vivo: Kinetics of hybridization, and concurrent changes in the histocompatibility profile of the tumor after propagation in different host strains

Abstract

Evidence of spontaneous fusion between Ehrlich ascites tumor (EAT) cells and host cells in vivo was derived from the appearance of host-specific T 6 chromosome markers in EAT cells after propagation in CBA/HT 6 mice. After 1 year of weekly passages, these hybrids lost some unidentified chromosomes, so that their modal chromosome number reverted to the original stem line mode of 68. Simultaneously, their incidence rose to a peak of 18% with no further change over a 4 year period. This increase was not explained by immunoselection pressure. Presumptive host cell nuclei in polynucleate cells in the EAT were of lymphocyte, monocyte and macrophage type. Since host-host cell heterokaryons were also noted, the observed tumor-host cell fusion may be a non-selective process. Nevertheless, this may be of biological importance, since concurrent changes in the hisocompatibility of the EAT were noted after propagation in different host strains. While the original EAT line (EAT- 0) maintained in CF 1 mice was highly tumorigenic by the subcutaneous (s.c.) route in CF 1 but not in CBA/HT 6 mice, i.p. propagation of the tumor in the latter strain (as two lines called EAT-2 and EAT-3) caused a progressive loss in s.c. tumorigenicity for CF 1 mice but a concurrent gain in tumorigenicity for CBA/HT 6 mice. When EAT- 3 was propagated into (CBA/HT 6 × C57B1/6)F 1 hybrids, this tumor (now called EAT- 4) retained s.c. tumorigenicity for the F 1 , but gradually lost its tumorigenicity for CBA/HT 6 mice and remained nontumorigenic for the C57B1/6 strain. Radioautographic examination of surface H- 2 antigens using a sandwich labeling with monospecific or polyvalent antisera revealed the presence of k and b antigens on EAT- 0 cells as well as somatic cells of CF 1 mice in which EAT- 0 was maintained. EAT- 3 long maintained in CBA/HT 6 (H- 2 k) mice showed the presence of k but not b antigens. After a propagation in F 1 (H- 2 kb) mice, EAT- 4 showed a moderate decline in the level of k but a small regain of b antigens, more evident after neuraminidase treatment. Subcutaneous tumors labeled more heavily for the host haplotype than the corresponding ascites tumors. The direction and time course of histocompatibility changes in the EAT were best explained by tumor-host cell fusion and chromosome loss.