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Influence of hyperbilirubinemia and phototherapy on markers of genotoxicity and apoptosis in full-term infants

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Abstract

Concerns of possible genotoxic effects of hyperbilirubinemia and phototherapy were raised from experimental and observational studies in neonates. This study aimed to assess the impact of hyperbilirubinemia and phototherapy on DNA damage and apoptosis in peripheral blood lymphocytes in healthy full-term infants. This study was conducted in the Children’s Hospital, Mansoura University. Patients enrolled in this study were classified into three groups (each with 45 full-term infants): group 1 was composed of infants with hyperbilirubinemia requiring phototherapy, group 2 infants with physiological jaundice not requiring phototherapy, and group 3 infants without clinical jaundice. All enrolled infants were subjected to assessment of DNA damage and apoptosis in peripheral blood lymphocytes, using the comet assay and P53 by flow cytometry, consecutively. In group 1, measurements were done twice, before starting phototherapy and just before its discontinuation. DNA damage was not significantly different in the three groups, but it significantly increased after exposure to phototherapy compared to pre-phototherapy levels. There was no significant difference in P53 level in the three groups; however, it significantly increased after exposure to phototherapy. There were significant positive correlations between the duration of phototherapy and markers of DNA damage and apoptosis.

Conclusions: Hyperbilirubinemia does not influence DNA damage and apoptosis, whereas phototherapy causes DNA damage and induces apoptosis in peripheral blood lymphocytes of full-term infants.

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Abbreviations

AAP:

American Academy of Pediatrics

LMPA:

Low melting point agarose

NMA:

Normal melting agarose

PBS:

Phosphate-buffered saline

SCE:

Sister chromatid exchange

TSB:

Total serum bilirubin

References

  1. Agarwal R, Deorari AK (2002) Unconjugated hyperbilirubinemia in newborns: current perspective. Indian Pediatr 39:30–42

    PubMed  Google Scholar 

  2. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia (2004) Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 114:297–316

    Article  Google Scholar 

  3. Anitha NT, Parkash C, Vishnu BB, Sridhar MG, Ramachandra RK (2013) Assessment of DNA damage in babies treated with phototherapy for neonatal jaundice. Curr Pediatr Res 17:45–47

    Google Scholar 

  4. Atici A, Bozkurt A, Muslu N, Eskandari HG, Turhan AH (2009) Oxidative stress under phototherapy. Turk J Pediatr 18:259–263

    Google Scholar 

  5. Aycicek A, Kocyigit A, Erel O, Senturk H (2008) Phototherapy causes DNA damage in peripheral mononuclear leukocytes in term infants. J Pediatr (Rio J) 84:141–146

    Article  Google Scholar 

  6. Christensen T, Kinn G, Granli T, Amundsen I (1994) Cells, bilirubin and light. Formation of photoproducts and cellular effects at defined wavelengths. Acta Paediatr 83:7–12

    Article  CAS  PubMed  Google Scholar 

  7. Christensen T, Reitan JB, Kinn G (1990) Single-strand breaks in the DNA of human cells exposed to visible light from phototherapy lamps in the presence and absence of bilirubin. J Photochem Photobiol B 7:337–346

    Article  CAS  PubMed  Google Scholar 

  8. Cole J, Skopek TR (1994) International Commission for Protection Against Environmental Mutagens and Carcinogens. Working paper no. 3. Somatic mutant frequency, mutation rates and mutational spectra in the human population in vivo. Mutat Res 304:33–105

    Article  CAS  PubMed  Google Scholar 

  9. Dean PN, Jett JH (1974) Mathematical analysis of DNA distributions derived from flow microfluorometry. J Cell Biol 60:523–527

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Dennery PA, Seidman DS, Stevenson DK (2001) Neonatal hyperbilirubinemia. N Engl J Med 344:581–590

    Article  CAS  PubMed  Google Scholar 

  11. El-Abdin MMYAE-SZ, Ibrhim MY, Koraa SSM, Mahmoud E (2012) Phototherapy and DNA changes in full-term neonates with hyperbilirubinemia. Egypt J Med Hum Genet 13:29–35

    Article  CAS  Google Scholar 

  12. Gathwala G, Sharma S (2000) Oxidative stress, phototherapy and the neonate. Indian J Pediatr 67:805–808

    Article  CAS  PubMed  Google Scholar 

  13. Giovannelli L, Pitozzi V, Riolo S, Dolara P (2003) Measurement of DNA breaks and oxidative damage in polymorphonuclear and mononuclear white blood cells: a novel approach using the comet assay. Mutat Res 538:71–80

    Article  CAS  PubMed  Google Scholar 

  14. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  CAS  PubMed  Google Scholar 

  15. Kahveci H, Dogan H, Karaman A, Caner I, Tastekin A, Ikbal M (2013) Phototherapy causes a transient DNA damage in jaundiced newborns. Drug Chem Toxicol 36:88–92

    Article  CAS  PubMed  Google Scholar 

  16. Karakukcu C, Ustdal M, Ozturk A, Baskol G, Saraymen R (2009) Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy. Mutat Res 680:12–16

    Article  CAS  PubMed  Google Scholar 

  17. Kuribayashi K, Finnberg N, Jeffers JR, Zambetti GP, El-Deiry WS (2011) The relative contribution of pro-apoptotic p53-target genes in the triggering of apoptosis following DNA damage in vitro and in vivo. Cell Cycle 10:2380–2389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Malayappan B, Garrett TJ, Segal M, Leeuwenburgh C (2007) Urinary analysis of 8-oxoguanine, 8-oxoguanosine, fapy-guanine and 8-oxo-2′-deoxyguanosine by high-performance liquid chromatography-electrospray tandem mass spectrometry as a measure of oxidative stress. J Chromatogr A 1167:54–62

    Article  CAS  PubMed  Google Scholar 

  19. Mohamed WA, Niazy WH (2012) Genotoxic effect of phototherapy in term newborn infants with hyperbilirubinemia. J Neonatal Perinatal Med 5:381–387

    Google Scholar 

  20. Møller P, Knudsen LE, Loft S, Wallin H (2000) The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors. Cancer Epidemiol Biomarkers Prev 9:1005–1015

    PubMed  Google Scholar 

  21. Nagata S (1997) Apoptosis by death factor. Cell 88:355–365

    Article  CAS  PubMed  Google Scholar 

  22. Ozkan H, Oren H, Tatli M, Ates H, Kumral A, Duman N (2008) Erythroid apoptosis in idiopathic neonatal jaundice. Pediatrics 121:1348–1351

    Article  Google Scholar 

  23. Porter ML, Dennis BL (2002) Hyperbilirubinemia in the term newborn. Am Fam Physician 65:599–606

    PubMed  Google Scholar 

  24. Renis M, Calandra L, Scifo C, Tomasello B, Cardile V, Vanella L, Bei R, La Fauci L, Galvano F (2008) Response of cell cycle/stress-related protein expression and DNA damage upon treatment of CaCo2 cells with anthocyanins. Br J Nutr 100:27–35

    Article  CAS  PubMed  Google Scholar 

  25. Roll EB (2005) Bilirubin-induced cell death during continuous and intermittent phototherapy and in the dark. Acta Paediatr 94:1437–1442

    Article  PubMed  Google Scholar 

  26. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  CAS  PubMed  Google Scholar 

  27. Sirchia G, Pizzi C, Scalamogna M (1972) A simple procedure for human lymphocyte isolation from peripheral blood. Tissue Antigens 2:139–140

    Article  CAS  PubMed  Google Scholar 

  28. Stocker R, Ames BN (1987) Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile. Proc Natl Acad Sci U S A 84:8130–8134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Tanaka K, Hashimoto H, Tachibana T, Ishikawa H, Ohki T (2008) Apoptosis in the small intestine of neonatal rat using blue light-emitting diode devices and conventional halogen-quartz devices in phototherapy. Pediatr Surg Int 24:837–842

    Article  PubMed  Google Scholar 

  30. Tatli MM, Minnet C, Kocyigit A, Karadag A (2008) Phototherapy increases DNA damage in lymphocytes of hyperbilirubinemic neonates. Mutat Res 654:93–95

    Article  CAS  PubMed  Google Scholar 

  31. Tridente A, Luca D (2012) Efficacy of light-emitting diode versus other light sources for treatment of neonatal hyperbilirubinemia: a systematic review and meta-analysis. Acta Paediatr 101:458–465

    Article  PubMed  Google Scholar 

  32. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J (2004) Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266:37–56

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Abd Elazeez Shabaan.

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Communicated by Patrick Van Reempts

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Yahia, S., Shabaan, A.E., Gouida, M. et al. Influence of hyperbilirubinemia and phototherapy on markers of genotoxicity and apoptosis in full-term infants. Eur J Pediatr 174, 459–464 (2015). https://doi.org/10.1007/s00431-014-2418-z

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  • DOI: https://doi.org/10.1007/s00431-014-2418-z

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