title: Photoactivated multivitamin preparation induces poly(ADP-ribosyl)ation, a DNA damage response in mammalian cells.
abstract: Multivitamin preparation (MVP) is part of total parenteral nutrition given to premature infants. Photoactivated MVP carries an important load in peroxides, but their cellular effects have not yet been determined. We hypothesized that these peroxides may elicit a DNA-damage response. We found that photoactivation of MVP and the resulting peroxide production were time-dependent and required the simultaneous presence of ascorbic acid and riboflavin. Cells treated with photoactivated MVP showed strongly stimulated poly(ADP-ribosyl)ation, an early DNA-damage response in mammals. Poly(ADP-ribosyl)ation stimulation was dependent on the presence of ascorbic acid and riboflavin in the photoactivated MVP. It did not occur in the presence of a specific PARP inhibitor nor in mouse fibroblasts deficient in PARP-1. Photoactivated MVP was able to induce single- and double-strand breaks in DNA, with a predominance of single-stand breaks. The presence of double-strand breaks was further confirmed using a 53PB1 focus analysis. Finally, photoactivated MVP was shown to be toxic to human cells and induced caspase-independent cell death. These results suggest that photoactivated MVP carries an important toxic load able to damage DNA and induce cell death. This study also emphasizes the importance of protecting MVP solution from light before use in preterm infants.
authors.affiliation: Department of Pediatrics, CHUQ-CHUL Research Center and Laval University, Quebec City, QC, Canada G1V 4G2.
authors.forename: Karine
authors.initials: K
authors.lastname: Zaniolo
authors.forename: Jean-François
authors.initials: JF
authors.lastname: St-Laurent
authors.forename: Steve N
authors.initials: SN
authors.lastname: Gagnon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lavoie
authors.forename: Serge
authors.initials: S
authors.lastname: Desnoyers
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000528:radiation effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008027:Light; D051379:Mice; D010289:Parenteral Nutrition, Total / Q000009:adverse effects; D010545:Peroxides / Q000633:toxicity*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism; D012256:Riboflavin / Q000528:radiation effects; D014815:Vitamins / Q000528:radiation effects*
chemical_list: D010545:Peroxides; D014815:Vitamins; D011064:Poly Adenosine Diphosphate Ribose; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D001205:Ascorbic Acid; D012256:Riboflavin