In vitro effects of anionic sulfur compounds on the spectrophotometric properties of native DNA.
Several anionic sulfur compounds are recognized as efficacious pretreatments for sulfur mustard (HD) poisoning. Our intent was to see if pretreatment compounds had a direct effect on DNA, a site where HD damage is thought to occur. A modification of the method of Szinicz et al. (Arzneim.-Forsch. 1981; 31: 1,713-1,717) was used to analyze the UV/VIS spectrum (205-400 nm) (n = 6) of calf thymus DNA (10-15 x 10(3) kDa) in the absence or presence of increasing concentrations of sodium thiosulfate, sodium 2-aminoethanethiosulfonate (thiotaurine), sodium metabisulfite or sodium sulfate. All compounds produced concentration-dependent absorbance decreases primarily at 212 nm, but also at 259 nm, with the exception of sodium sulfate. For example, 8.36 x 10(-4) M sodium thiosulfate reduced the absorbance of DNA at 212 nm by >60%. The kinetics of sulfur compounds on native DNA need further study. We propose that these anionic sulfur compounds interact with DNA possibly by changing the topology of this macromolecule. Effects may be due to interactions of these sulfur compounds at higher concentrations with DNA, with resulting ligand-DNA supercoiling. This process could protect against HD intoxication, which is caused in part by the uncoiling of DNA.
Baskin
S I
SI
Division of Pharmacology, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Prabhaharan
V
V
Bowman
J D
JD
Novak
M J
MJ
D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003879:Dermatologic Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008024:Ligands; D009151:Mustard Gas / Q000633:toxicity*; D013053:Spectrophotometry; D013457:Sulfur Compounds / Q000494:pharmacology*; D013885:Thiosulfates / Q000494:pharmacology; D013950:Thymus Gland
D003879:Dermatologic Agents; D008024:Ligands; D013457:Sulfur Compounds; D013885:Thiosulfates; D004247:DNA; D009151:Mustard Gas