Role of lead-binding proteins in renal cancer.
High-dose lead exposure in rodents has been shown to produce pathognomonic lead intranuclear inclusion bodies and to result in an increased incidence of renal adenocarcinomas. Studies from this laboratory and others have demonstrated the presence of high-affinity renal lead-binding proteins in rat kidneys which act as tissue sinks for lead at low dose levels. Cell-free nuclear translocation studies have shown that these molecules are capable of facilitating the intranuclear movement of lead and that they are associated with chromatin. These data suggest that renal lead-binding proteins may play a role in mediating known alterations in renal gene expression associated with formation of intranuclear inclusion bodies. More recent studies from this laboratory have demonstrated the presence of chemically similar lead-binding proteins in kidneys of both monkeys and humans. Such observations suggest that a similar mechanism may be operating in primates since lead intranuclear inclusion bodies are also observed in these species. These data provide a testable mechanistic approach for assessing the possible role(s) of lead-binding proteins in mediating the intranuclear movement of lead and lead-induced renal cancer in primate species.
Program in Toxicology, School of Medicine, University of Maryland, Baltimore.
B A
BA
Fowler
M W
MW
Kahng
D R
DR
Smith
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D007854:Lead / Q000378:metabolism*; D011323:Primates; D011485:Protein Binding; D012377:Rodentia
D002352:Carrier Proteins; C055217:lead-binding proteins; D007854:Lead