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-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 microM) 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 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-glucuronosyltransferase(s) determined in permeabilized hepatocytes. Cryopreserved hepatocytes fully retained a high capacity to glucuronidate the benzo[a]pyrene phenol.
Richter
P
P
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08854-5930.
Kauffman
F C
FC
Zaleski
J
J
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D015925:Cryopreservation; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism
D001580:Benzopyrenes; D005965:Glucuronates; D013431:Sulfates; C032136:1-hydroxybenzo(a)pyrene; D014453:Glucuronosyltransferase