A comparison of the effect of lead nitrate on rat liver chromatin, DNA and histone proteins in solution.
Although lead is widely recognized as a toxic substance in the environment and directly damage DNA, no studies are available on lead interaction with chromatin and histone proteins. In this work, we have examined the effect of lead nitrate on EDTA-soluble chromatin (SE chromatin), DNA and histones in solution using absorption and fluorescence spectroscopy, thermal denaturation and gel electrophoresis techniques. The results demonstrate that lead nitrate binds with higher affinity to chromatin than to DNA and produces an insoluble complex as monitored at 400 nm. Binding of lead to DNA decreases its Tm, increases its fluorescence intensity and exhibits hypochromicity at 210 nm which reveal that both DNA bases and the backbone participate in the lead-DNA interaction. Lead also binds strongly to histone proteins in the absence of DNA. The results suggest that although lead destabilizes DNA structure, in the chromatin, the binding of lead introduces some sort of compaction and aggregation, and the histone proteins play a key role in this aspect. This chromatin condensation, upon lead exposure, in turn may decrease fidelity of DNA, and inhibits DNA and RNA synthesis, the process that introduces lead toxicity at the chromatin level.
Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran. rabbani@ibb.ut.ac.ir
Azra
A
Rabbani-Chadegani
Sayeh
S
Abdosamadi
Nesa
N
Fani
Shayesteh
S
Mohammadian
D000818:Animals; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004492:Edetic Acid / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004785:Environmental Pollutants / Q000633:toxicity; D006657:Histones / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D009566:Nitrates / Q000633:toxicity*; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D051381:Rats; D012995:Solubility; D013057:Spectrum Analysis; D013696:Temperature
D002843:Chromatin; D004785:Environmental Pollutants; D006657:Histones; D009566:Nitrates; D007854:Lead; C017461:lead nitrate; D004247:DNA; D004492:Edetic Acid