Effects of dimethyl sulfoxide on the gene induction of cytochrome P450 isoforms, UGT-dependent glucuronosyl transferase isoforms, and ABCB1 in primary culture of human hepatocytes

Biol Pharm Bull. 2003 Jul;26(7):1052-6. doi: 10.1248/bpb.26.1052.

Abstract

We investigated the gene expression of GAPDH, cytochrome P450 isoforms (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7), UGT-dependent glucuronosyl transferase isoforms (UGT1A6 and UGT1A9), and ABC transporter (ABCB1) after exposure to 0.1, 0.5, and 2.5% dimethyl sulfoxide (DMSO). GAPDH mRNA levels after exposure were less than 2 times higher or lower than control levels at all DMSO concentrations. CYP1A1, CYP1B1, CYP2A6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, and UGT1A9 mRNA levels were less than 2 times higher or lower than control levels at 0.1% and 0.5% DMSO. CYP1A2, UGT1A6, and ABCB1 mRNA levels were less than 2 times higher or lower than control levels at all DMSO concentrations. CYP2E1 and CYP3A4 mRNA levels were 2.5-3.2 times and 2.0-3.3 times higher than control levels at 2.5% DMSO, respectively. UGT1A9 mRNA levels were 0.2-0.5 times lower than control levels at 2.5% DMSO. Exposure to beta-naphthoflavone reduced CYP1A1 mRNA levels in a concentration-dependent manner for donors 1 and 2. Exposure to beta-naphthoflavone reduced CYP1A2 mRNA levels in a concentration-dependent manner for all donors. However, exposure to beta-naphthoflavone increased CYP1B1 mRNA levels for donors 2 and 3 at 2.5% DMSO. Exposure to rifampicin reduced CYP3A4 mRNA levels for all donors at 0.5% and 2.5% DMSO. Exposure to rifampicin also reduced CYP3A5 and CYP3A7 mRNA levels for donors 1 and 3 at 0.5% and 2.5% DMSO. In conclusion, a DMSO concentration of 0.1% or less may be appropriate for studying induction after drug exposure.

MeSH terms

  • ATP-Binding Cassette Transporters / biosynthesis*
  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Aged
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Dimethyl Sulfoxide / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / physiology
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / genetics
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology*
  • Humans
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcriptional Activation

Substances

  • ATP-Binding Cassette Transporters
  • Isoenzymes
  • RNA, Messenger
  • Cytochrome P-450 Enzyme System
  • UDP-glucuronosyltransferase, UGT1A6
  • Glucuronosyltransferase
  • Dimethyl Sulfoxide