Effect of Phototherapy on Hepatic Microsomal Drug Metabolism in Heterozygous and Homozygous Gunn Rats

  • B. R. Sonawane
  • B. Granati
  • L. Chiandetti
  • F. F. Rubaltelli
  • T. R. C. Sisson
  • S. J. Yaffe


Phototherapy for the treatment and prevention of neonatal infant jaundice is widely practiced. The effectiveness of photo-therapy in reducing hyperbilirubinemia in jaundiced infants is very well established,12 however, its widespread use has raised some doubts and concerns about its safety.3 Although, the short-term effects of phototherapy for the most part are minimal4, fluorescent light has been shown to be both toxic5 and mutagenic6 to mammalian cells. It has been demonstrated that visible light (450nm) is able to induce genetic changes in prokaryotic as well as eukaryotic cells7 and that the illumination of isolated DNA in the presence of bilirubin and/or riboflavin8–9 resulted in alterations in the physical and biochemical properties of this biopolymer. Gantt et a1 1 0 reported that cool-white fluorescent light exposure resulted in both DNA damage and chromatid breaks in mouse cells. Futhermore, Speck and Rosenkranz11 reported structural changes in the DNA isolated from human cells grown in culture after exposure to high intensity illumination in the absence of added photosensitizers.


Chromatid Break Aniline Hydroxylase Unconjugated Hyperbilirubinemia Blue Light Exposure Microsomal Drug Metabolism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. F. Lucey, M. Ferreiro, and J. Hewitt, Prevention of hyperbilirubinemia of prematurity by phototherapy, Pediatrics 41: 1047–1054, 1968.PubMedGoogle Scholar
  2. 2.
    S. O. Porto, R. S. Pildes, and H. Goodman, Studies on the effect of phototherapy on neonatal hyperbilirubinemia among low birth weight infants, J. Pediatr. 75: 1045–1047, 1969.PubMedCrossRefGoogle Scholar
  3. 3.
    R. E. Behrman, A. I. Brown, M. R. Currie, J. W. Hastings, G. B. Odell, R. Shaffer, R. B. Setlow, T. B. Vogl, F. J. Wurtman, R. J. Anderson, H. J. Kostkowski, and A. P. Simopoulos, J. Pediatr. 84: 135, 1974.CrossRefGoogle Scholar
  4. 4.
    J. H. Drew, K. J. Marriage, V. V. Bayle, E. Bajraszewski, and J. M. McNamara, Phototherapy, short-and long-term complications, Arch. Dis. Childn. 51: 454–458, 1976.CrossRefGoogle Scholar
  5. 5.
    B. T. Noxon and R. J. Wang, Formation of photo products lethal for human cells in culture by daylight, fluorescent light and bilirubin light, Photochem. Photobiol. 26: 589–593, 1977.CrossRefGoogle Scholar
  6. 6.
    M. 0. Bradley and N. A. Sharkey, Mutagenicity and toxicity of visible fluorescent light to cultured mammalian cells, Nature (London) 266: 724–726, 1977.CrossRefGoogle Scholar
  7. 7.
    W. T. Speck and H. S. Rosenkranz, Base substitution mutations induced in Salmonella strains by visible light (450nm), Photochem. Photobiol. 21: 369, 1975.PubMedCrossRefGoogle Scholar
  8. 8.
    W. T. Speck, C. C. Chen, and H. S. Rosenkranz, In vitro studies of the effects of light and riboflavin on DNA and HeLa cells, Pediat. Res. 9: 150, 1975.PubMedCrossRefGoogle Scholar
  9. 9.
    W. T. Speck and H. S. Rosenkranz, The bilirubin inducedphotodegradation of DNA, Pediat. Res. 9: 703, 1975.PubMedCrossRefGoogle Scholar
  10. 10.
    R. Gantt, R. Parshad, R. A. G. Ewing, K. K. Sanford, G. M. Jones, R. E. Tarone, and K. W. Kohn Fluorescent light induced DNA Cross linkage and chromatid breaks in mouse cells in culture, Proc. Natl. Acad. Sci. U.S.A. 75: 3809–3812, 1978.PubMedCrossRefGoogle Scholar
  11. 11.
    W. T. Speck and H. S. Rosenkranz, Intracellular deoxyribonucleic acid-modifying activity of phototherapy lights, Pediat. Res. 10: 553–555, 1976.PubMedCrossRefGoogle Scholar
  12. 12.
    B. F. Erlanger, Photoregulation of biologically active macromolecules, Ann. Rev. Biochem. 45: 267–283, 1976.CrossRefGoogle Scholar
  13. 13.
    G. Montiagnoli, Biological effects of light on proteins: Enzyme activity modulation, Photochem. Photobiol. 26: 679–683, 1977.CrossRefGoogle Scholar
  14. 14.
    D. H. Hug, The activation of enzymes with light, Photochem. Photobiol. Rev. 3: 1–33, 1978.CrossRefGoogle Scholar
  15. 15.
    D. H. Hug, Photoactivation of enzymes, Photochem. Photobiol. Rev. 6: 87–138, 1981.CrossRefGoogle Scholar
  16. 16.
    R. A. Yeary, K. J. Wise, and D. R. Davis, Activation of hepatic microsomal glucuronyltransferase from Gunn rats by exposure to light, Life Science 17: 1887–1890.. 1976.CrossRefGoogle Scholar
  17. 17.
    T. R. C. Sisson, B. Granati, R. Sonawane, and T. Fiorentino, Effect of light on enzyme activity in the perfused Gunn rat liver. Abstr. Am. Soc. Photobiol. 1978: 98.Google Scholar
  18. 18.
    A. W. Girotti, Bilirubin-sensitized photoinactivation of enzymes in the isolated membrane of the human erythrocyte. Photochem. Photobiol. 24: 525–532, 1976.PubMedCrossRefGoogle Scholar
  19. 19.
    M. Orzalesi, G. Natoli, A. Panero, and M. Ciocca, Plasma hepatic enzyme in jaundiced newborn infants treated with phototherapy, Birth Defects Orig. Article Ser. 12(2)93–99, 1976.Google Scholar
  20. 20.
    C. Dacou-Voutetakis, D. Anagnostakis, and N. Matsaniotis, Effect of prolonged illumination (phototherapy) on concentration of luteinizing hormone in human infants. Science 199: 1229–1231, 1978.PubMedCrossRefGoogle Scholar
  21. 21.
    B. Lemaitre, P. L. Toubas, M. Guillot, C. Dreux, and J. P. Relier Changes of serum gonadotropin concentrations in Premature babies submitted to phototherapy. Biol. Neonate 32: 113–118, 1977.PubMedCrossRefGoogle Scholar
  22. 22.
    L. F. Soyka, W. G. Hunt, J. F. Lucey, Effect of phototherapy on hepatic microsomal drug metabolizing activity of rats, Ped. Res. (abstracts) 9: 287, 1975.Google Scholar
  23. 23.
    V. Nair and R. Casper, The influence of light on daily rhythm in hepatic drug metabolizing enzymes in the rat, Life Sci. 8: 1291–1298, 1969.Google Scholar
  24. 24.
    D. R. Davis, R. A. Yeary, and G. Randall, Effects of special blue fluorescent light on hepatic mixed-function oxidase activity in the rat., Pediatr. Pharmacol. 1: 313–319, 1981.Google Scholar
  25. 25.
    G. W. Lucier, O. S. McDaniel, J. R. Bend, and E. Faeder, Effects of hycanthone and two of its chlorinated analogues on hepatic microsomes, J. Pharmacol. Exp. Ther. 186: 416–424, 1973.PubMedGoogle Scholar
  26. 26.
    T. Omura and R. Sato, The carbon-monoxide binding pigment of liver microsomes. I. Evidence for its hemoprotein nature, J. Biol. Chem. 239: 2370–2378, 1964.PubMedGoogle Scholar
  27. 27.
    G. W. Lucier, B. R. Sonawane, and 0. S. McDaniel, Glucuronidation and deglucuronidation reactions in hepatic and extrahepatic tissues during perinated development, Drug Metal. Dispos. 5: 279–288, 1977.Google Scholar
  28. 28.
    J. E. Gielen, F. M. Goujon, and D. W. Nebert, Genetic regulation of aryl hydrocarbon hydroxylase induction, J. Biol. Chem. 247: 1125–1137, 1972.PubMedGoogle Scholar
  29. 29.
    R. L. Dixon, L. G. Hart, L. A. Rogers, and J. R. Fouts, The metabolism of drugs by liver microsomes from alloxandiabetic rats: longterm diabetes., J. Pharmac. Exp. Ther. 142: 312–319, 1963.Google Scholar
  30. 30.
    S. Orrenius, On the mechanism of drug hydroxylation in rat liver microsomes, J. Cell Biol. 26: 713–723, 1965.PubMedCrossRefGoogle Scholar
  31. 31.
    K. J. Netter and G. Seidel, An adaptively stimulated 0-demethylating system in rat liver microsomes and its kinetic properties, J. Pharmacol. Exp. Ther. 146: 61, 1064.Google Scholar
  32. 32.
    H. Lowry, N. J. Rosebrough, A. L. Farr and R. J. Randall, Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265–275, 1951.Google Scholar
  33. 33.
    A. N. Cohn and J. D. Ostrow, New concepts in phototherapy: photoisomerization of bilirubin IX and potential toxic effects of lights, Pediatrics 65: 740–749, 1980Google Scholar
  34. 34.
    F. Rubaltelli and B. Granati, Phototherapy of neonatal hyperbilirubinemia, Med Biol. Environ. 8: 185–195, 1980.Google Scholar
  35. 35.
    T. R. C. Sisson, B. Slaven, and P. B. Hamilton, Birth Defects, Original Article Series, 6, 122, 1976.Google Scholar
  36. 36.
    T. R. C. Sisson and M. Wickler Transmission of light through living tissues (abstract) Pediat. Res. 7: 316, 1973.Google Scholar
  37. 37.
    A. Jr. Windorfer, G. Faxelius, and L. 0. Boreus, Studies on phototherapy in newborn infants. Influence on protein binding of bilirubin salicylate and on activity of acetylsalicyclate acid esterage, ACTA Pediatrica Scandinavica, 2: 293–298, 1975.CrossRefGoogle Scholar
  38. 38.
    R. J. Strasser and W. L. Butler, Interactions of flavins with cytochrome c and oxygen in excited artificial systems, in The Blue Light Syndrome. (H. Senger, ed.), pp. 25–29, SpringerVerlag, Berlin/Heidelberg/New York, 1980Google Scholar
  39. 39.
    W. L. Butler, The mediation of redox changes by photoreceptor pigments, paper presented at the International Conference on the Effect of Blue Light in Plants and Microorganisms, Marburg, July 1979.Google Scholar
  40. 40.
    H. Senger, 0. Klein, and D. Dornemann, The action of blue light on 5-aminolaevulinic acid formation, in, The Blue Light Syndrome (H. Senger, ed.), pp. 541–551, Springer-Verlag, Berlin/ Heidelberg/New York, 1980.Google Scholar
  41. 41.
    J. A. Schiff, Blue light and the photocontrol of chloroplast developement in Euglena, in, The Blue Light Syndrome (H. Senger, ed.), pp. 495–511, Springer-Verlag, Berlin/Heidelberg/New York, 1980.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • B. R. Sonawane
    • 1
  • B. Granati
    • 2
  • L. Chiandetti
    • 2
  • F. F. Rubaltelli
    • 2
  • T. R. C. Sisson
    • 3
  • S. J. Yaffe
    • 4
  1. 1.Department of Pediatrics and Animal BiologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of PediatricsUniversity of PadovaPadovaItaly
  3. 3.Rutgers Medical SchoolNew BrunswickUSA
  4. 4.Center for Research for Mothers and Children National Institutes of HealthBethesdaUSA

Personalised recommendations