Dose-dependent induction or depression of cysteine conjugate beta-lyase in rat kidney by N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine

Toxicology. 1993 Jan 29;77(1-2):133-44. doi: 10.1016/0300-483x(93)90144-h.


The influence of N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine (NAc-PCBD) on cysteine conjugate beta-lyase in female rat kidney has been examined. After a single, non-nephrotoxic dose of NAc-PCBD (3 mg/kg), cytosolic beta-lyase enzyme activity was increased 1.5 to 3-fold commensurate with a corresponding increase in enzyme protein levels as assessed by both Western blot and ELISA analyses. Using a cDNA probe for beta-lyase, this induction was found to be accompanied by an increase in the cognate mRNA. In contrast, a higher, nephrotoxic dose of NAc-PCBD (10 mg/kg) decreased all the above parameters. These effects appeared to be specific to the cytosolic form of the enzyme as no changes in kidney mitochondrial beta-lyase or enzyme protein levels were observed. Repeated dosing with the lower dose level (3 mg/kg) resulted in either no change, or in some instances, a reduction in the above parameters, suggesting an accumulation of the xenobiotic and a masking of the induction phenomenon. The molecular mechanisms underlying these observations are discussed in terms of the nephrotoxicity of halogenated xenobiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / toxicity
  • Animals
  • Blood Urea Nitrogen
  • Blotting, Western
  • Butadienes / administration & dosage
  • Butadienes / toxicity*
  • Carbon-Sulfur Lyases*
  • Cytosol / enzymology
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Injections, Intraperitoneal
  • Kidney / drug effects*
  • Kidney / enzymology*
  • Lyases / analysis
  • Lyases / biosynthesis*
  • Mitochondria / enzymology
  • RNA, Messenger / analysis
  • Rats
  • Transaminases / analysis


  • Butadienes
  • RNA, Messenger
  • N-acetyl-S-pentachloro-1,3-butadienylcysteine
  • Transaminases
  • glutamine-pyruvate aminotransferase
  • Lyases
  • Carbon-Sulfur Lyases
  • S-alkylcysteine lyase
  • Acetylcysteine