LEAD SUPPRESSES CHIMERIC HUMAN TRANSFERRIN GENE-EXPRESSION IN TRANSGENIC MOUSE-LIVER

The major iron-transport protein in serum is transferrin (TF) which al so has the capacity to transport other metals. This report presents ev idence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl tran sferase (CAT) genes received lead or sodium salts by intraperitoneal i njections or in drinking water. Transgene expression in liver was supp ressed 31 to 50% by the lead treatment. Lead regulates human TF transg enes at the mRNA level since liver CA T enzyme activity, CA T protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did n ot alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket im munoelectrophoresis of mouse sera. Moderate levels of lead exposure we re sufficient to evoke the human TF transgene response; blood lead lev els in mice that received lead acetate in drinking water ranged from 3 0 mug/dl to 56 mug/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protei n in cultured human hepatoma HepG2 cells. The regulation of human TF a pparently differs from the regulation of mouse TF which is unresponsiv e to lead exposure. (C) 1993 Intox Press, Inc.