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Lead effects on protamine–DNA binding
Author(s) -
QuintanillaVega Betzabet,
Hoover Dennis,
Bal Wojciech,
Silbergeld Ellen K.,
Waalkes Michael P.,
Anderson Larry D.
Publication year - 2000
Publication title -
american journal of industrial medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.7
H-Index - 104
eISSN - 1097-0274
pISSN - 0271-3586
DOI - 10.1002/1097-0274(200009)38:3<324::aid-ajim12>3.0.co;2-r
Subject(s) - protamine , dna , chromatin , dna damage , binding site , in vitro , biophysics , medicine , microbiology and biotechnology , biology , biochemistry , heparin
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 Pb 2+ and Zn 2+ (as chloride salts). They also provided evidence that thiol groups mainly participate for Zn 2+ ‐binding; however, HP2 has additional binding sites for Pb 2+ . 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. Am. J. Ind. Med. 37:324–329, 2000. © 2000 Wiley‐Liss, Inc.