Predominance of glucuronidation over sulfation in metabolism of 1-hydroxybenzo[a]pyrene by isolated rat hepatocytes

Add time:07/20/2019    Source:sciencedirect.com

This study shows that 1-hydroxybenzo[a]pyrene glucuronide and 1-hydroxybenzo[a]pyrene sulfate are formed in isolated rat hepatocytes. Formation of these conjugates by hepatocytes incubated with 1-acetoxy-[G-3H]benzo[a]pyrene (100 μM) as a source of intracellular 1-hydroxy-[G-3H]benzo[a]pyrene was documented by comparison of the spectra of metabolites separated by HPLC with the spectra of 1-hydroxybenzo[a]pyrene glucuronide and 1-hydroxybenzo[a] pyrene sulfate standards. The rates of 1-hydroxybenzo[a]pyrene glucuronidation and sulfation were 7.72 ± 1.03 and 0.68 ± 0.02 nmol × mg dry wt.−1 × 30 min−1, respectively. The rate of 1-hydroxybenzo[a]pyrene glucuronide production by intact cells corresponded well with the total activity of UDP-glucuronosyltransferase(s) determined in permeabilized hepatocytes. Cryopreserved hepatocytes fully retained a high capacity to glucuronidate the benzo[a]pyrene phenol.

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