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. 1994 Sep;102(Suppl 3):115–116. doi: 10.1289/ehp.94102s3115

Role of lead-binding proteins in renal cancer.

B A Fowler 1, M W Kahng 1, D R Smith 1
PMCID: PMC1567412  PMID: 7843083

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker E. L., Jr, Goyer R. A., Fowler B. A., Khettry U., Bernard D. B., Adler S., White R. D., Babayan R., Feldman R. G. Occupational lead exposure, nephropathy, and renal cancer. Am J Ind Med. 1980;1(2):139–148. doi: 10.1002/ajim.4700010204. [DOI] [PubMed] [Google Scholar]
  2. Choie D. D., Richter G. W. Cell proliferation in mouse kidney induced by lead. I. Synthesis of deoxyribonucleic acid. Lab Invest. 1974 May;30(5):647–651. [PubMed] [Google Scholar]
  3. Choie D. D., Richter G. W. Cell proliferation in rat kidneys after prolonged treatment with lead. Am J Pathol. 1972 Aug;68(2):359–370. [PMC free article] [PubMed] [Google Scholar]
  4. Choie D. D., Richter G. W. Dell proliferation in mouse kidney induced by lead. II. Synthesis of ribonucleic acid and protein. Lab Invest. 1974 May;30(5):652–656. [PubMed] [Google Scholar]
  5. Fowler B. A., DuVal G. Effects of lead on the kidney: roles of high-affinity lead-binding proteins. Environ Health Perspect. 1991 Feb;91:77–80. doi: 10.1289/ehp.919177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fowler B. A., Kahng M. W., Smith D. R., Conner E. A., Laughlin N. K. Implications of lead binding proteins for risk assessment of lead exposure. J Expo Anal Environ Epidemiol. 1993 Oct-Dec;3(4):441–448. [PubMed] [Google Scholar]
  7. Fowler B. A., Mahaffey K. R. Interactions among lead, cadmium, and arsenic in relation to porphyrin excretion patterns. Environ Health Perspect. 1978 Aug;25:87–90. doi: 10.1289/ehp.782587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lilis R. Long-term occupational lead exposure, chronic nephropathy, and renal cancer: a case report. Am J Ind Med. 1981;2(3):293–297. doi: 10.1002/ajim.4700020309. [DOI] [PubMed] [Google Scholar]
  9. Mistry P., Lucier G. W., Fowler B. A. High-affinity lead binding proteins in rat kidney cytosol mediate cell-free nuclear translocation of lead. J Pharmacol Exp Ther. 1985 Feb;232(2):462–469. [PubMed] [Google Scholar]
  10. Mistry P., Mastri C., Fowler B. A. Influence of metal ions on renal cytosolic lead-binding proteins and nuclear uptake of lead in the kidney. Biochem Pharmacol. 1986 Feb 15;35(4):711–713. doi: 10.1016/0006-2952(86)90371-0. [DOI] [PubMed] [Google Scholar]
  11. Oskarsson A., Squibb K. S., Fowler B. A. Intracellular binding of lead in the kidney: the partial isolation and characterization of postmitochondrial lead binding components. Biochem Biophys Res Commun. 1982 Jan 15;104(1):290–298. doi: 10.1016/0006-291x(82)91973-8. [DOI] [PubMed] [Google Scholar]
  12. Selevan S. G., Landrigan P. J., Stern F. B., Jones J. H. Mortality of lead smelter workers. Am J Epidemiol. 1985 Oct;122(4):673–683. doi: 10.1093/oxfordjournals.aje.a114146. [DOI] [PubMed] [Google Scholar]

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