title: Novel synthetic (S,S) and (R,R)-secoisolariciresinol diglucosides (SDGs) protect naked plasmid and genomic DNA From gamma radiation damage.
abstract: Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed. However, extraction methods are complex and are associated with low yield and high costs. Using a novel synthetic pathway, our group succeeded in chemically synthesizing SDG (S,S and R,R enantiomers), which faithfully recapitulates the properties of their natural counterparts, possessing strong antioxidant and free radical scavenging properties. This study further extends initial findings by now investigating the DNA-radioprotective properties of the synthetic SDG enantiomers compared to the commercial SDG. DNA radioprotection was assessed by cell-free systems such as: (a) plasmid relaxation assay to determine the extent of the supercoiled (SC) converted to open-circular (OC) plasmid DNA (pBR322) after exposure of the plasmid to gamma radiation; and (b) determining the extent of genomic DNA fragmentation. Exposure of plasmid DNA to 25 Gy of γ radiation resulted in decreased supercoiled form and increased open-circular form, indicating radiation-induced DNA damage. Synthetic SDG (S,S) and SDG (R,R), and commercial SDG at concentrations of 25-250 μM significantly and equipotently reduced the radiation-induced supercoiled to open-circular plasmid DNA in a dose-dependent conversion. In addition, exposure of calf thymus DNA to 50 Gy of gamma radiation resulted in DNA fragments of low-molecular weight (<6,000 bps), which was prevented in a dose-dependence manner by all synthetic and natural SDG enantomers, at concentrations as low as 0.5 μM. These novel results demonstrated that synthetic SDG (S,S) and SDG (R,R) isomers and commercial SDG possess DNA-radioprotective properties. Such properties along with their antioxidant and free radical scavenging activity, reported earlier, suggest that SDGs are promising candidates for radioprotection for normal tissue damage as a result of accidental exposure during radiation therapy for cancer treatment.
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Pulmonary, Allergy and Critical Care Division, Philadelphia, Pennsylvania 19104.
authors.forename: Om P
authors.initials: OP
authors.lastname: Mishra
authors.forename: Ralph
authors.initials: R
authors.lastname: Pietrofesa
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
mesh_terms: D000818:Animals; D002072:Butylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004278:DNA, Superhelical / Q000737:chemistry / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D016678:Genome / Q000235:genetics*; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008970:Molecular Weight; D010957:Plasmids / Q000235:genetics*; D011837:Radiation-Protective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D002072:Butylene Glycols; D004278:DNA, Superhelical; D005960:Glucosides; D011837:Radiation-Protective Agents; D004247:DNA; C090142:secoisolariciresinol diglucoside