Potential for Genetic Damage from Multivitamin Solutions Exposed to Phototherapy Illumination

Ennever, John F.; Carr, Howard S.; Speck, William T.

doi:10.1203/00006450-198303000-00004

Cited by 16 publications

(9 citation statements)

References 11 publications

(14 reference statements)

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“…The weak affinity of RB for nucleic acid is consistent with the finding of Kuratomi and Kobayashi (16) that only one RB molecule is bound to every 500 nucleotide base pairs of DNA in solutions of low ionic strength. Weak RB–DNA binding is also consistent with reports that RB sensitizes the formation of both RB–nucleic acid adducts and single strand breaks (17,18). Our attempts to measure a binding constant of RB via a Scatchard analysis was unsuccessful because of the weak binding of the dye.…”

Section: Discussionsupporting

confidence: 90%

Binding Affinities of Commonly Employed Sensitizers of Viral Inactivation¶

Dardare¹,

Platz²

2007

Photochemistry and Photobiology

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Methylene blue (MB), riboflavin (RB) and psoralen sensitizers (4′ aminomethyl‐4,5′,8‐trimethylpsoralen [AMT] and derivatives) are under study as sensitizers of viral inactivation of blood products such as plasma proteins, platelets and red cells, all of which lack genomic nucleic acid. To predict where these sensitizers accumulate in viruses and in cells, their relative affinities for calf thymus DNA, neutral and negatively charged phospholipids and albumin were determined by dialysis. MB has a strong affinity for nucleic acid and negatively charged phospholipid, but little affinity for albumin or neutral phospholipid. RB has modest affinity for nucleic acid and little affinity for albumin or either phospholipid. AMT has substantial affinity for nucleic acid, neutral and negatively charged phospholipids and albumin. Neither AMT nor RB binds to poly G, although MB has some affinity for this polymer. Evidence of association of RB with guanosine monophosphate, adenosine monophosphate and tryptophan methylester hydrochloride in PBS buffer in the presence and absence of formamide was obtained from nonlinear Stern–Volmer plots and shifts in the ground state absorption spectrum of RB.

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Section: Discussionsupporting

confidence: 90%

Binding Affinities of Commonly Employed Sensitizers of Viral Inactivation¶

Dardare¹,

Platz²

2007

Photochemistry and Photobiology

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“…Photolysis of riboflavin and nucleic acids leads to the formation of flavin adducts to AT rich regions of DNA and to the generation of single-strand breaks. − The single-strand breaks may well be due to the action of superoxide anion or hydrogen peroxide, ,− which are also formed upon photolysis of riboflavin. Riboflavin and light sensitize the killing of mammalian cells. , Analysis of the nucleic acids of these cells reveals guanine oxidation and strand breaks. , Interest in this photochemistry has recently surged due to reports that riboflavin can sensitize the inactivation of viruses in the presence of transfusable blood products with acceptable recovery of plasma protein, platelet, and red cell function…”

Section: Introductionmentioning

confidence: 99%

The Photochemistry of Riboflavin Tetraacetate and Nucleosides. A Study Using Density Functional Theory, Laser Flash Photolysis, Fluorescence, UV−Vis, and Time Resolved Infrared Spectroscopy

et al. 2002

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The photoreaction between riboflavin tetraacetate and nucleosides was investigated using time-resolved infrared spectroscopy (TRIR), laser flash photolysis with UV−vis detection, fluorescence quenching, absorption spectroscopy, and density functional theory calculations. Riboflavin tetraacetate (RBTA) was studied experimentally with indole and with Sheu and Foote's organic soluble silylated guanosine (G‘). Lumiflavin and (R)-2-amino-(S)-4-hydroxy-(R)-5-(hydroxymethyl)-tetrahydrofuran were used as computational models for RBTA and for the sugar moiety of the nucleoside, respectively, using density functional theory calculations (B3LYP/6-31G* and B3LYP/6-31+G**). Vibrational spectra were also calculated for the transient species. Time-resolved infrared spectroscopic data obtained using RBTA are in excellent agreement with the calculated spectra for the triplet flavin, and in the presence of silylated guanosine, with the formation of the most stable hydroflavin radical, RBTH, by an electron transfer−proton transfer mechanism. Although the gas-phase calculations indicate that abstraction of a hydrogen atom from the sugar is slightly exothermic, this reaction does not proceed at a rate measurable as monitored by TRIR spectroscopy. Singlet RBTA is also quenched by G‘ in methylene chloride. Stern−Volmer analysis of the fluorescence quenching data indicates that this reaction proceeds with a rate constant of 8.7 × 108 M-1 s-1.

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“…Riboflavin has been implicated in toxicity when taken as part of a standard multivitamin preparation. In this situation, riboflavin may be involved in photodynamic damage to DNA, but only in synergism with other multivitamin components, because it has been shown that high levels of riboflavin alone are unable to damage DNA [33].…”

Section: Discussionmentioning

confidence: 99%

Comparison of a Direct and Indirect Method for Measuring Flavins-Assessing Flavin Status in Patients Receiving Total Parenteral Nutrition

Hamilton

Woodside²,

McIlveen³

et al. 2009

TOCCHEMJ

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Background: Riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are cofactors in oxidation-reduction reactions. The aim of this study was to compare a direct high performance liquid chromatography (HPLC) method with an indirect enzymatic method to assess flavin status and establish reference intervals. The HPLC method was used to assess prevalence of flavin deficiency in total parenteral nutrition (TPN) patients. Method: Blood was obtained from 90 healthy volunteers and 51 TPN patients. Results for each method were compared using Spearmans Rank correlation. Results from reference groups and TPN patients were compared using Mann-Whitney U tests. Results: Erythrocyte glutathione reductase activity coefficients (EGRAC) correlated with flavin levels measured by HPLC (p<0.001). HPLC was chosen for TPN samples analyses due to superior sensitivity. There was no significant difference between FAD and FMN levels in controls and TPN patients, although TPN patients had significantly higher levels of riboflavin than controls (p<0.001). Conclusion: HPLC is superior to the EGRAC assay for assessing flavin status. Hyporiboflavinosis is not prevalent in TPN patients.

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Potential for Genetic Damage from Multivitamin Solutions Exposed to Phototherapy Illumination

Cited by 16 publications

References 11 publications

Binding Affinities of Commonly Employed Sensitizers of Viral Inactivation¶

Binding Affinities of Commonly Employed Sensitizers of Viral Inactivation¶

The Photochemistry of Riboflavin Tetraacetate and Nucleosides. A Study Using Density Functional Theory, Laser Flash Photolysis, Fluorescence, UV−Vis, and Time Resolved Infrared Spectroscopy

Comparison of a Direct and Indirect Method for Measuring Flavins-Assessing Flavin Status in Patients Receiving Total Parenteral Nutrition

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