Lead effects on protamine-DNA binding

Betzabet Quintanilla-Vega, Dennis Hoover, Wojciech Bal, Ellen K. Silbergeld, Michael P. Waalkes, Larry D. Anderson

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Background: Lead impairs male fertility and may affect offspring of exposed males, but the mechanisms for this impairment are not completely clear. Protamine P1 and P2 families pack and protect mammalian sperm DNA. Human HP2 is a zinc-protein and may have an important role in fertility. As lead has affinity for zinc-containing proteins, we evaluated its ability in vitro to bind to HP2 and its effects on HP2-DNA binding. Methods and Results: UV/VIS spectroscopic data indicated that HP2 binds both Pb2+ and Zn2+(as chloride salts). They also provided evidence that thiol groups mainly participate for Zn2+-binding; however, HP2 has additional binding sites for Pb2+. The mobility shift assay showed that lead interaction with HP2 caused a dose-dependent decrease on HP2 binding to DNA, suggesting that lead may alter chromatin stability. Conclusions: These in vitro results demonstrate that lead can interact with HP2 altering the DNA-protamine binding. This chemical interaction of lead with protamines may result in chromatin alterations, which in turn may lead to male fertility problems and eventually to DNA damage. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)324-329
Number of pages6
JournalAmerican Journal of Industrial Medicine
Issue number3
StatePublished - 2000
Externally publishedYes


  • Lead toxicity
  • Protamines
  • Reproductive toxicity
  • Sperm chromatin

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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