Changes of CYP1A1, GST, and ALDH3 enzymes in hepatoma cell lines undergoing enhanced lipid peroxidation

Hepatoma cells show alterations in the response to oxidative stress (decrea sed lipid peroxidation) and in xenobiotic metabolism enzymes (decreased P45 0, increased GST and ALDH3). This study examined the effect of lipid peroxi dation on the expression of the above enzymes in two rat hepatoma cell line s (MH1C1 and 7777). To induce oxidative stress, cells were exposed to arach idonic acid (to increase lipid peroxidation substrate) and/or to beta -naph thoflavone (to increase CYP450), and treated with one dose of iron/histidin e. The cells, that were still viable after the challenge, were refed with t he culture medium and CYP1A1, GST, and ALDH3 enzymes monitored for 1, 6, 12 , and 24 h. Treatments that increased markers indicative of lipid peroxidat ion are associated with a decrease in enzyme activities, which was permanen t for CYP1A1 and transient for the other enzymes. We speculate from these d ata that aldehydic byproducts of lipid peroxidation may be responsible for these effects. Thus, restoration of lipid peroxidation in hepatoma cells se ems to induce a rapid adaptation to oxidative stress, which is achieved by a simultaneous decrease of reactive oxygen species production and an increa se in the two main enzymes involved in the removal of the aldehydic product s of lipid peroxidation. (C) 2000 Elsevier Science Inc.