CHARACTERIZATION OF MBT-2 TUMOR-CELL VARIANT RESISTANT TO TUMOR-NECROSIS-FACTOR

Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 "variant" tumour cell population emerged in vitro. This concurred with the finding of transient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant "variant" MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of "variant" MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.