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Published on: September 5, 2017
Photoactivated multivitamin preparation induces poly(ADP-ribosyl)ation, a DNA damage response in mammalian cells
Karine Zaniolo1, Jean-François St-Laurent, Steve N Gagnon
1Department of Pediatrics, CHUQ-CHUL Research Center and Laval University, Quebec City, QC, Canada G1V 4G2.
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.
Insights
Photoactivated multivitamin preparation (MVP) generates peroxides, damaging infant DNA and causing cell death. Protect MVP from light before use in preterm infants to prevent these harmful effects.
Area of Science:
- Biochemistry
- Cell Biology
- Neonatal Nutrition
Background:
- Multivitamin preparations (MVP) are essential components of total parenteral nutrition for premature infants.
- Photoactivation of MVP can generate peroxides, but their cellular impact, particularly on DNA, remains largely undetermined.
Purpose of the Study:
- To investigate the cellular effects of peroxides produced by photoactivated MVP.
- To determine if photoactivated MVP elicits a DNA-damage response and induces cell death in human cells.
Main Methods:
- Assessed peroxide production in MVP upon photoactivation, dependent on ascorbic acid and riboflavin.
- Measured poly(ADP-ribosyl)ation (PARP activity) as a DNA-damage response marker in cells treated with photoactivated MVP.
- Quantified DNA strand breaks (single and double) using assays and 53BP1 focus analysis.
- Evaluated cellular toxicity and cell death mechanisms (caspase-independent) in response to photoactivated MVP.
Main Results:
- Photoactivation of MVP, requiring ascorbic acid and riboflavin, led to time-dependent peroxide production.
- Photoactivated MVP significantly stimulated poly(ADP-ribosyl)ation, indicating DNA damage, in a manner dependent on ascorbic acid, riboflavin, and PARP-1.
- Photoactivated MVP induced both single- and double-strand DNA breaks, confirmed by 53BP1 foci.
- Treated human cells exhibited toxicity and caspase-independent cell death.
Conclusions:
- Photoactivated MVP generates toxic peroxides that damage DNA and induce cell death in human cells.
- The findings highlight the critical need to protect multivitamin preparations from light exposure before administration to preterm infants.
- This study underscores the potential risks associated with photo-degraded MVPs in neonatal care.
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