THE EFFECTS OF LONG-TERM ADMINISTRATION OF 3-THIA FATTY-ACID, A PEROXISOME PROLIFERATOR, TO MORRIS-7800-C1 HEPATOMA-CELLS

Morris 7800 C1 hepatoma cells were grown in the presence of 80 muM tet radecylthioacetic acid (TTA), a peroxisome proliferator, for 1 year (l ong-term-treated cells). The growth of the Morris 7800 C1 hepatoma cel ls 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 g rowth inhibition was easily reversed by insulin (0.4 muM). 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 f or 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 wit h 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.