Effects of 5-fluorouracil and leucovorin in spheroids: a model for solid tumours.

We determined the cytotoxcity of 5FU alone or with leucovorin in MGH-U1 cells growing as monolayers or spheroids. The 5FU IC50 in spheroid and monolayers was 100 microM in both culture systems. The IC50 of 5FU and 5FU and 100 microM leucovorin in spheroids and monolayers was 100 microM and 50 microM, respectively. [H3]5 FU reached cells at all depths of the spheroid viable rim. Cells isolated from increasing depths of the spheroid viable rim demonstrated increasing resistance to 5FU. 5FU cytotoxicity is increased by leucovorin in monolayer but not spheroids, penetration is not limiting in 5FU cytotoxicity in spheroids and there is increasing resistance to 5FU in the viable rim.