Effect of NRTI exposures on extracellular lactate levels. HepG2 cell cultures were exposed to concentrations 10- or 100-fold higher than the Cmax levels of the NRTIs listed, and the levels of lactate in the media were determined after 5, 10, or 15 days. Lactate levels were normalized according to cell numbers. Values represent the percentage of 0.1% DMSO vehicle-only control cultures and represent the means ± the SEM of three to six independent experiments. The duration of culture was 5 days (▪), 10 days (░⃞), and 15 days (□). *, P < 0.05; **, P < 0.001 (Dunnett's multiple-comparison test). Levels greater than 300% were truncated to enhance presentation and were for, ddC-treated cells, 824 ± 136% and 875 ± 116% of the vehicle-treated control values for 10 and 100 times the Cmax, respectively, and for 100-fold the Cmax (for LVD) was 335% ± 28% of the vehicle-treated control.