Morris 7800 C1 hepatoma cells were grown in the presence of 80 microM tetradecylthioacetic acid (TTA), a peroxisome proliferator, for 1 year (long-term-treated cells). The growth of the Morris 7800 C1 hepatoma cells was inhibited in cells treated with TTA for up to 8 days. Treatment of the cells with TTA for 1 year did not reduce growth further. The growth inhibition was easily reversed by insulin (0.4 microM). Peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity was increased 5.5 times in cells treated with TTA for 3 days. In the cells treated with TTA for 1 year the ACO activity was increased only two times. A similar ACO mRNA half-life (two times the control) was found in cells treated with TTA for 1 year and for 3 days. This implies a loss of effect of TTA on the transcription rate of the ACO gene in long-term-treated cells.