Jan 1, 1984

Glucuronide conjugation reduces the cytotoxicity but not the mutagenicity of benzo(a)pyrene in the CHO/HGPRT assay

Teratogenesis, Carcinogenesis, and Mutagenesis
Leslie Recio, A W Hsie

Abstract

Benzo(a)pyrene (B[a]P) is biotransformed by the mixed-function oxidase (MFO) system to numerous metabolites some of which are cytotoxic and/or mutagenic to mammalian cells. However, conjugation of B(a)P metabolites with glucuronic acid in vivo is a major pathway of detoxication and elimination. The effects of glucuronide conjugation on B(a)P-induced cytotoxicity and mutagenicity were studied using the CHO/HGPRT assay with a rat liver homogenate preparation containing MFO system cofactors (S9 mix) and uridine diphosphate alpha-D-glucuronic acid (UDPGA). B(a)P metabolites proximate to the biologically active B(a)P quinones (B[a]P 6-OH) and to the B(a)P 7,8-diol-9,10 epoxide isomers (B[a]P 7,8-diol), were also assayed with S9 mix in the absence and presence of UDPGA. The addition of UDPGA to S9 mix reduced B(a)P-induced cytotoxicity but did not affect mutagenicity. B(a)P 6-OH-mediated cytotoxicity was also reduced in the presence of UDPGA. UDPGA had no effect on B(a)P 7,8-diol-induced cytotoxicity or mutagenicity. B(a)P phenols have been shown to be the preferred B(a)P-metabolite substrates for UDP-glucuronyltransferase enzymes. Thus, the reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely d...Continue Reading

  • References19
  • Citations8

References

  • References19
  • Citations8

Citations

Mentioned in this Paper

Cricetulus
Structure-Activity Relationship
Glucuronic Acid, 6-(14)C-labeled, (D)-isomer
Ovary
Glucuronic Acids
Microsomes, Liver
Benzo(a)pyrene
Cell Survival
Metabolic Biotransformation
Mixed Function Oxygenases

About this Paper

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