Variability in the expression of xenobiotic-metabolizing enzymes during the growth cycle of rat hepatoma cells

Abstract

1. The activity of various xenobiotic-metabolizing enzymes was examined throughout the growth cycle (16 d) of the well-differentiated rat hepatoma cell line C2Rev7.

2. Cytochrome P-450-dependent aldrin epoxidase activity showed a peak on day 3 after plating of cells and decreased by more than 90% during the following six days.

3. Glutathione S-transferase and UDP-glucuronosyl transferase with 4-hydroxybiphenyl as substrate also showed decreases in their activities towards the later phase of the growth cycle, although to lesser extents than the mono-oxygenase.

4. The activity of cytochrome c reductase and of the UDP-glucuronosyl transferase with 3-hydroxybenzo[a]pyrene as substrate remained constant throughout the growth cycle.

5. Aldrin epoxidase activities varied markedly with the number of cells plated.

6. The results suggest that the balance of activating and inactivating pathways may vary considerably during the growth cycle of differentiated hepatoma cells. This should be taken into account when standardizing these cells as test systems for the assessment of cytotoxic and genotoxic chemicals.