Differential expression of CYP1A1 and CYP1A2 genes in H4IIE rat hepatoma cells exposed to TCDD and PAHs

Environ Toxicol Pharmacol. 2015 Jan;39(1):358-68. doi: 10.1016/j.etap.2014.11.031. Epub 2014 Dec 10.

Abstract

Rat hepatoma cells H4IIE were treated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs) (dibenz(a,h)anthracene, benzo(a)pyrene, benz(a)anthracene, chrysene), low-concentration mixtures of PAHs and TCDD, and environmental mixtures contaminated by PAHs and their derivatives. Expression of the gene battery comprising cytochrome P450 Cyp1a1, Cyp1a2, Cyp1b1, and glutathione-s-transferase Gsta2 and Gstp was investigated using quantitative real time polymerase chain reaction (qRT-PCR) analysis. The results revealed that TCDD induce Cyp1a1>Cyp1a2>Cyp1b1, while PAHs and PAH-containing environmental mixtures induce Cyp1a2>Cyp1a1>Cyp1b1 gene expression pattern. While low-concentration mixtures elicited a more pronounced response in comparison to single treatments, the typical gene expression patterns were not observed. In all samples, Gsta2 was predominantly expressed relative to Gstp. These findings indicate that differential Cyp1a1 and Cyp1a2 expression in the H4IIE cells might be used for detection of PAHs in highly contaminated environmental mixtures, but not in low-concentration mixtures of these compounds.

Keywords: CYP; Gene expression; H4IIE; Mixtures; PAHs; TCDD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Cell Line, Tumor
  • Cytochrome P-450 CYP1A1 / genetics*
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP1B1 / genetics
  • Cytochromes / genetics*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glutathione S-Transferase pi / genetics
  • Glutathione Transferase / genetics
  • Isoenzymes / genetics
  • Liver Neoplasms / genetics
  • Polychlorinated Dibenzodioxins / toxicity*
  • Polycyclic Aromatic Hydrocarbons / toxicity*
  • Rats

Substances

  • Cytochromes
  • Isoenzymes
  • Polychlorinated Dibenzodioxins
  • Polycyclic Aromatic Hydrocarbons
  • Cyp1a2 protein, rat
  • Cyp1b1 protein, rat
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP1B1
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Gstp1 protein, rat
  • glutathione S-transferase alpha