The role of african american ethnicity and metabolism in sentinel polychlorinated biphenyl congener serum levels.
Polychlorinated biphenyls (PCBs) are environmental contaminants found in the serum of human populations across the globe. A small set of sentinel PCB congeners (IUPAC# 101, 118, 138, 153, and 180) commonly sought in human serum are often used as markers of exposure. The Chicago Great Lakes cohort of pregnant African American women was developed to study organochlorine exposure through Great Lakes resources in a pregnant African American population and their children. Comparison of PCB serum concentrations in women reporting mixed race/ethnicity within the cohort shows significant elevations of serum PCB 101 and 118 in women reporting exclusive African American ancestry.Incubations were performed using pooled human liver microsomes followed by individual recombinant human CYP isoform microsomes to identify whether the other sentinel congeners are metabolized by human CYP 450. In human liver microsome metabolism experiments with the sentinel PCB congeners (IUPAC# 101, 118, 138, 153, and 180), only PCB 101 metabolism produced an identifiable metabolite. However, a significant loss of parent compound was observed for PCB 118 incubations with human liver microsomes. The loss of PCB 101 and PCB 118 in microsome experiments indicates they are likely metabolized in human liver. Therefore, CYP 450 mediated metabolic differences may contribute to differences in serum concentrations by race/ethnicity.PCB metabolism has an important impact on toxicity. PCB metabolites have been shown to differ significantly in toxicity profiles relative to parent compounds. Biomonitoring studies of PCB serum levels have correlated with toxicity for the metabolizeable congeners such as PCB 101 and PCB 118. However, measureable amounts of metabolizeable parent congeners such as PCB 101 may not be detectable in the serum of study participants. Because PCB 118 is metabolized, but is also readily found in human serum, it may be a better marker of metabolism related PCB toxicity. Human specific PCB metabolism is difficult to characterize but has important pathophysiological ramifications and deserves further study.
McGraw
Joseph E
JE
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois USA 60612.
Waller
Donald P
DP