Effect of lovastatin pre-treatment on viability at clinically attainable concentrations. (A) Viability as assessed by Trypan blue staining: HL60 cells were treated with 1, 3 or 12 mM lovastatin on Day 0. Mevalonate (200 mM) was added to the cells on day 1, 2, 3, 4 or 5. The effects on viability determined on day 6 as measured by cell counts and Trypan blue uptake. N¼ 2; one example is shown. (B) Ability to recover from lovastatin after 72 h of exposure. HL60 or U937 cells were exposed to lovastatin for 72 h and then rescued with mevalonate (200 mM). They were allowed to proliferate for an additional 6 days. The IC50 was determined after a total of 3 days of lovastatin exposure and 6 days of mevalonate-rescued growth, i.e. on day 9. Two separate assays were performed and the results for each are as shown (N¼ 2 for each cell line, with the individual samples indicated by “A” or “B”). For comparison purposes, the IC50 values as determined previously are plotted (same data as Figure 2, day 6).