Carcinogenicity of Tumor Cell Populations: Origin of a Putative H-2 Isoantigenic Loss Variant Tumor23

Abstract

The properties of an unusual mouse tumor capable of extremely rapid and widespread spontaneous metastatic growth were recently described; this tumor, called MDAY-D2, at first appeared to be an H-2K^k loss variant of an (A×DBA/2)F₁ (H-2K^kD^d × K^dD^d) sarcoma called MDAY and was obtained by serial ip passage of MDAY in DBA/2 (K^dD^d) mice. The studies described here were concerned with the analysis of the origin of MDAY-D2; i.e., was it a true variant or a newly induced DBA/2 tumor? Several approaches were used, most of which exploited defined cell surface alloantigenic systems as natural genetic markers. The results indicated that MDAY-D2 was indeed a newly induced DBA/2 tumor and, furthermore, that MDAY was a homozygous A-strain tumor, probably a T-cell lymphoma. Thus a) MDAY was found to be Ly-1.2⁺, Ly-2.2⁺, and Thy-1.2⁺ but Ly-6.2⁻, whereas the opposite pattern was observed with MDAY-D2; b) MDAY possessed the private and public H-2 specificities associated with H-2K^k and H-2D^d, but not H-2D^k [i.e., it typed as an A-strain (H-2^a) tumor, not as (A × DBA/2)F₁]; c) MDAY-D2 possessed private and public specificities associated with H-2K^d and H-2D^d and was found to be H-2K^k-negative [i.e., it typed as a DBA/2 (H-2^d) tumor]; d) serial injection of clonally derived ouabain-resistant H-2K^k-positive MDAY cells into DBA/2 hosts led to the rapid development of an MDAY-D2 (H-2^d-positive) tumor that was fully ouabain-sensitive. Several findings did not support a contaminant theory to explain induction of MDAY-D2. The rapid induction of a tumor after injection of allogeneic tumor cells may have importance in relation to oncogenesis, tumor variant formation, and tumor progression. The results showed that tumor cells themselves can be potent carcinogens.