Induction of cytochrome P450 1A1 in human hepatoma HepG2 cells by 6-nitrochrysene.

The present study has determined the effects of 6-nitrochrysene (6-NC) on human cytochrome P450-dependent monooxygenases in human hepatoma HepG2 cells. Treatment of HepG2 cells with 6-NC increased the activities of microsomal benzo[a]pyrene hydroxylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylases, cytosolic glutathione S-transferase and N-acetyltransferase, and S9 metabolic activation of 6-NC in the Ames mutagenicity test. Immunoblot and RNA blot analyses revealed that 6-NC induced CYP1A1 protein and mRNA levels in the hepatoma cells. Nuclear transcription assay demonstrated that 6-NC increased the transcription rate of CYP1A1 gene in HepG2 cells. Treatment of human lung carcinoma NCI-H322 cells with 6-NC increased benzo[a]pyrene hydroxylase activity and CYP1A1 protein and mRNA levels. These results demonstrate that 6-NC is an inducer of human CYP1A1 and the induction occurs at a transcriptional level in HepG2 cells. The ability of 6-NC to induce liver and lung CYP1A1 may be an important factor to consider in assessing 6-NC metabolism and toxicity in humans.