In vitro and in vivo responses of a panel of murine colon tumours to TCNU: a positive correlation

Abstract

TCNU is highly active against a panel of three histologically distinct transplantable murine adenocarcinomas of the colon (MAC tumours). Significant reductions in colony formation (greater than 70%) were observed in vitro in all three cell lines following a 1 h exposure to TCNU at experimentally achievable drug C X t values. A good correlation exists between in vivo tumour responses and in vitro cell responses in all cases. Dose-response curves generated at increasing exposure times suggest that no active or long lived products of TCNU are formed as a result of the drug's spontaneous breakdown in vitro (rate of breakdown was 0.078 micrograms min-1 at 37 degrees C). Preliminary studies with the HT-29 human colon cell line have demonstrated that multi-cellular spheroids are more responsive to TCNU (2 X) than the same cells cultured as monolayers.