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

Abstract

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.

• Authors: R M Chen, M W Chou, T H Ueng
• Journal: Toxicology letters (Toxicol Lett) Vol. 117 Issue 1-2 Pg. 69-77 (Sep 30 2000) ISSN: 0378-4274 [Print] Netherlands
• PMID: 11033235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chrysenes
• RNA, Messenger
• Methylcholanthrene
• 6-nitrochrysene
• Benzopyrene Hydroxylase
• Cytochrome P-450 CYP1A1

Topics

• Benzopyrene Hydroxylase (drug effects, metabolism)
• Carcinoma, Hepatocellular (enzymology, pathology)
• Chrysenes (pharmacology)
• Cytochrome P-450 CYP1A1 (biosynthesis, drug effects, genetics)
• Dose-Response Relationship, Drug
• Enzyme Induction (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Methylcholanthrene (pharmacology)
• Microsomes (drug effects, enzymology)
• RNA, Messenger (drug effects, genetics, metabolism)
• Time Factors
• Tumor Cells, Cultured (cytology, drug effects, enzymology)