PREDOMINANCE OF GLUCURONIDATION OVER SULFATION IN METABOLISM OF 1-HYDROXYBENZO[A]PYRENE BY ISOLATED RAT HEPATOCYTES

This study shows that 1-hydroxybenzo[a]pyrene glucuronide and 1-hydrox ybenzo[a]pyrene sulfate are formed in isolated rat hepatocytes. Format ion of these conjugates by hepatocytes incubated with 1-acetoxy-[G-H-3 ]benzo[a]pyrene (100 mu M) as a source of intracellular 1-hydroxy-[G-H -3]benzo[a]pyrene was documented by comparison of the spectra of metab olites separated by HPLC with the spectra of 1-hydroxybenzo[a]pyrene g lucuronide 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 x mg dry wt.(-1) X 30 min(-1), respectively . The rate of 1-hydroxybenzo[a]pyrene glucuronide production by intact cells corresponded well with the total activity of UDP-glucuronosyltr ansferase(s) determined in permeabilized hepatocytes. Cryopreserved he patocytes fully retained a high capacity to glucuronidate the benzo[a] pyrene phenol.