PMID: 20650074Apr 1, 1995Paper

Production of cyclophosphamide metabolites by primary hepatocyte cultures from male and pregnant rats: Effect of Aroclor 1254 pretreatment

Toxicology in Vitro : an International Journal Published in Association with BIBRA
L A VanaertsJ Noordhoek

Abstract

In a previous paper (VanAerts et al., Toxicology in Vitro 1993, 7, 769-775) we have shown that the embryotoxicity of Cyclophosphamide was greatly enhanced when Cyclophosphamide had been added to a primary hepatocyte culture derived from Aroclor 1254-pretreated male rats (M(A)) and the medium from this culture was added to a post-implantation rat embryo culture. However, when medium from hepatocytes that had been derived from untreated male rats (M(C)), untreated pregnant rats (P(C)) or Aroclor 1254-pretreated pregnant rats (P(A)) was used embryotoxicity was low. We now present data on the concentrations of 4-ketocyclophosphamide, carboxyphosphamide and nornitrogen mustard in the primary hepatocyte culture media. 4-Ketocyclophosphamide was absent in media from P(C) or P(A) and present in low concentrations in media from M(C) and M(A). Carboxyphosphamide and nornitrogen mustard were present in all media, but their concentrations were several times higher in medium from M(A) than in media from other sources. This indicates that Aroclor 1254 pretreatment enhances Cyclophosphamide metabolism much more in male rats than in pregnant rats. It is suggested that both a greater inducibility of CYP2B1 and augmented stabilization of 4-hydro...Continue Reading

References

Jan 1, 1978·Biochemical Pharmacology·R A DeitrichJ Schmuck
Feb 1, 1975·The Biochemical Journal·N KaplowitzG Clifton
Jan 1, 1992·Critical Reviews in Biochemistry and Molecular Biology·R Lindahl
Jan 1, 1988·Pharmacology & Therapeutics·N E Sladek
Jun 15, 1973·Biochemical Pharmacology·M G Neale, D V Parke
Nov 1, 1980·Biochemical Pharmacology·B E Domeyer, N E Sladek
Nov 1, 1993·Toxicology in Vitro : an International Journal Published in Association with BIBRA·L A van AertsJ Noordhoek

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Citations

Jul 11, 2001·Toxicologic Pathology·L L ArnoldS M Cohen

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