QUANTITATIVE COMPARISON BETWEEN THE TRANSPLANTABILITY OF HUMAN AND MURINE TUMORS INTO THE BRAIN OF NCR SED-NU/NU NUDE AND SEVERE COMBINED IMMUNODEFICIENT MICE/

We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1 993) that the take rate of human xenografts in the s.c. tissue of seve re combined immunodeficient (SCID) mice is significantly higher than t hat of nude mice. Earlier, this laboratory reported that the transplan tability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of h uman and murine tumors in comparison with s.c. tissue in SCID mice; (b ) the relative i.c. transplantability in SCID mice in comparison to nu de mice; and (c) the influence of whole-body irradiation on i.c. trans plantability of SCID and nude mice. The assay based on the number of c ells required to transplant tumors into 50% of recipients (TD50) was u sed to describe the transplantability assays. Five human and four muri ne tumor cell lines were used. Concurrent TD50 assays were performed i .c. in whole-body irradiated and non-irradiated SCID and nude mice. Se rial 2-10-fold dilutions of cells were injected in a 10-mul volume int o the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50s were significantly lower than th e s.c. TD50s by a factor of 1.7-1580. The average enhancement ratio (s .c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No signi ficant difference was found between the i.c. TD50s in SCID and in nude mice, contrary to the significant difference in s.c. TD50s between bo th strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 199 3). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID m ice. In conclusion, despite the significantly lower s.c. TD50s of huma n xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immun oreactivities between nude and SCID mice in s.c. transplantability; ho wever, for i.c. transplantability, nude mice behaved equally as well a s SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immuno reactivity, although the immunoreactivity is significantly lower than that of nude mice.