Lead effects on protamine-DNA binding

Background Lead impairs male fertility and may affect offspring of exposed males, bur the mechanisms for this impairment are not completely cleat: Pro tamine P1 and P2 families pack and protect mammalian sperm DNA, Human HP2 i s a zinc-protein and may have art important role in fertility. As lean 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 bind ing sites for Pb2+. The mobility shift assay showed that lead interaction w ith 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 w ith protamines may result in chromatin alterations, which in turn may lead to male fertility problems and eventually to DNA damage. Am. J. Ind. Med. 3 8:324-329, 2000. (C) 2000 Wiley-Liss, Inc.