Haemopoietic Lineage Sensitivity and Individual Susceptibility to PCB126: Relation to Glutathione S-transferase μ

Abstract

The effect of PCB126 on the in vitro growth potential of human myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells derived from human cord blood haemopoietic cells was examined. The possible link between individual variability in susceptibility and the presence of the xenobiotic metabolizing enzyme glutathione S-transferase class mu (GST μ) was studied. After density centrifugation separation, mononuclear cord blood cells were cultured in the presence of PCB126 (10 −6 m and 10 −8 m). Several cord blood samples were simultaneously tested for: (1) colony formation and (2) the presence of the GST μ gene measured by PCR. An interindividual variability in the response to PCB126 was present. At 10 −8 m and 10 −6 m PCB126, respectively 8 (40%) and 10 (50%) out of 20 cord blood samples showed a significant dose-dependent decrease in CFU-GM numbers. Erythroid progenitors were less affected by PCB126. At 10 −8 m and 10 −6 m PCB126, respectively only two (12%) and three (18%) out of 17 cord blood samples showed a significant decrease in BFU-E numbers. The presence or absence of the GST μ gene was determined using PCR. The GST μ gene was present in 52% (14 out of 27 samples tested) of the cord blood samples. Damage to the myeloid and erythroid haemopoietic progenitor cells at either PCB126 concentrations was not correlated with the presence of the GST μ gene.