Tumor bed expression in xenografted artificial heterogeneous colon tumors

Artificial heterogeneous xenograft tumors (AHTs) were produced by injecting admixtures of two clonal cell lines (A and D) originally isolated from the DLD-1 human colon adenocarcinoma. The volumetric growth of unirradiated pure A or D tumors and 2 different admixtures (approximately 90% A + 10% D or 10% A + 90% D) were compared to growth of similar tumors growing in normal tissue stroma that had received 5, 10, or 15 Gy of X rays 1 day prior to cell injections. The X-irradiations produced a dose dependent delay in growth at sizes of 500 mm3 (designated as the tumor bed effect, TBE) for both pure and admixed tumors of about 2 at 15 Gy. There were no significant differences in TBE among the various groups. Also, determination of tumor cell yields, or colony forming efficiencies, showed no differences among tumors growing in undamaged or damaged stroma. However, beginning at about 20 days postirradiation, there was a significant change in the percentage composition of the tumors growing in the irradiated stroma. Both admixtures became significantly enriched in the subpopulation that was originally predominant. In contrast, the percentage compositions of the admixtures growing in unirradiated stroma remained stable over the duration of the experiment period (to about 70 days postirradiation). We interpret these data to indicate that the radiation damage to the normal tissue produced an intratumor environment leading to competitive exclusion dynamics of the minority subpopulation. Clinical implications of these results are discussed.