Comparative sensitivity of cells from human tumors and derivative tumor xenografts to radiation and heat treatments.

Abstract

Human tumor xenografts in athymic mice are often used to study the efficacy of cancer treatments, but it is not known whether the xenografts accurately reflect the treatment responsiveness of the original tumors. To assess the validity of tumor xenografts as specific models of neoplastic disease, a soft-agar colony assay was used to compare the sensitivity of cells from surgical tumor specimens and derivative xenograft lines to various radiation and heat treatments in vitro. Xenograft lines were established from melanomas and from carcinomas of the bladder, breast, cervix, and colon. Single-cell suspensions from the original tumors and the corresponding tumor xenografts were subjected to treatments that measured inherent radiation sensitivity, split-dose radiation repair capacity, low-dose-rate radiation sensitivity, inherent heat sensitivity, capacity for development of thermotolerance, and sensitivity to step-down heating (treatment at 43.5 degrees C followed by treatment at 41.5 degrees C). Cell survival curves were plotted for each treatment, and a two-tailed Student's t test was used to search for statistically significant correlations between the curves. Although cells from different surgical tumor specimens varied widely in their sensitivity to radiation and heat treatments, there was always a statistically significant correlation (P < .05) between the sensitivity of cells from the surgical specimens and the corresponding tumor xenografts. These observations strongly suggest that intrinsic properties of human tumor cells generally are retained during serial heterotransplantation. Thus, human tumor xenograft lines may be valuable tools in studies aimed at identifying cellular properties of importance for the clinical treatment sensitivity of human cancer. This does not necessarily mean, however, that the treatment responsiveness of the xenografts in vivo mirrors the clinical treatment responsiveness of the tumors in patients.