Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver

Journal Article · · Neurotoxicology (Park Forest South, Illinois); (United States)

OSTI ID:5544971

Adrian, G S; Rivera, E V; Adrian, E K; Lu, Y; Buchanan, J; Herbert, D C; Weaker, F J; Walter, C A; Bowman, B H ^[1]

---

1. Univ. of Texas Health Science Center, San Antonio (United States)

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.

• OSTI ID: 5544971
• Journal Information: Neurotoxicology (Park Forest South, Illinois); (United States), Journal Name: Neurotoxicology (Park Forest South, Illinois); (United States) Vol. 14:2-3; ISSN 0161-813X; ISSN NRTXDN
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
CHIMERAS
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ENZYME ACTIVITY
GENE REGULATION
GLANDS
GLOBULINS
GLOBULINS-BETA
LEAD
LIVER
MAMMALS
METALLOPROTEINS
METALS
MICE
MOSAICISM
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RESPONSE MODIFYING FACTORS
RODENTS
SYNTHESIS
TRANSFERRIN
TRANSGENIC ANIMALS
TRANSGENIC MICE
VERTEBRATES