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Phototoxic effects of bilirubin
NEWS AND VIEWS
373
Instruments that measure IR luminescence during continuous illumination operate on the time integral of eqn. (1) which leads to L = b’k,T*&&
(1 -
lo-Ax)
wave (4)
from which we see that TA influences the observed signal amplitude and, as above, conditions that decrease rA will adversely affect the signal. As stated above, most red-light-absorbing sensitizers have weak, but significant, fluorescence intensity in the spectral region where O,( ‘Ag) emits. Thus luminescence spectral measurements invariably show the singlet oxygen peak sitting atop a significant background. As rA decreases the 1.27 pm peak tends to disappear into this background and be indistinguishable therefrom. One possibility for picking out the (presumably) longer-lived singlet oxygen emission is to use a phase-sensitive detection system and frequencymodulated illumination. In this way rapidly decaying fluorescence can be separated from slower-decaying luminescence by taking advantage of the resulting phase differences. Such a method has been described and used [2 ] for demonstrating 1.27 pm luminescence from red-light-illuminated, porphyrin-containing tissue samples. As with the other techniques, the phase modulation method suffers progressively as rA shortens owing to quenching processes. Of course, given optimum sensitivity and observational bandwidth it would be surprising if the combination of light, sensitizer and oxygen did not produce singlet oxygen. The next generation of experiments must attempt to quantify O,( ‘As) yields and correlate them with damage to tissue, cell death, and effects at the organelle level. For these demands to be effectively carried out, a new generation of instruments having high sensitivity at higher bandwidth needs to be developed. 1 M. A. J. Rodgers, Singlet oxygen quantum yields. In J. R. Heitz and K. R. Downum (eds.), Light Activated Pesticides, A. C. S. Symp. Ser. 339, Washington, DC, 1987, pp. 76 - 97. 2 J. G. Parker, Optical monitoring of singlet oxygen generation during photodynamic treatment of tumors, IEEE Circuits and Deuices Magazine, (January, 1987) 10 - 21.
Phototoxic
effects of bilirubin
T. CHRISTENSEN Medical Section, (Norway)
and J. B. REITAN National Znstitute
Phototherapy safe and efficient
of Radiation
Hygiene,
P.O. Box 55, N-1345
OsterBs
of neonatal jaundice is widely used and is regarded as a way of reducing the bilirubin concentration in different
374
NEWS AND VIEWS
tissues. The bilirubin is able to participate in a number of photochemical reactions. Some of them lead to the facilitated excretion of bilirubin, but it has recently been shown that some may also be potentially harmful to the infant [ 1 - 31. The exact mechanism behind the therapeutic effect has been debated, but today there is a general agreement that photoisomerization of bilirubin is the main photochemical mechanism for converting bilirubin to a more water-soluble and excretable form. Isomerizations to geometric and structural isomers are the most quantum-efficient processes, but photo-oxidation may take place as well. Under particular conditions in vitro cytotoxic photoproducts are formed. These are quite long lived and can cause cell death accompanied by single-strand breaks in the DNA and mutations in hamster cells. Of course such biological effects cause some worry about the safety of phototherapy. However, at the moment the deleterious effects seen in cell cultures have only been looked for in a limited number of cell types and under particular culture conditions. An open question is for example why the effects seem only to be produced in media containing calf serum or in the absence of serum, and not in human serum. If it is accepted that oxidation products formed by self-sensitized photo-oxidation of bilirubin are responsible for the toxic effects in vitro, the mode of binding of bilirubin in different tissues is important. None of the toxic effects are observed in the presence of human serum, and therefore bilirubin in the blood circulation seems not to represent a risk. Too little is known about how bilirubin is bound in other tissues. The phototoxic effects have been shown using blue light. Other wavelengths such as green light will be tested. From general experience with light effects, it can be assumed that green light may be safer and it has been shown that it may even be effective in therapy [ 41. Phototherapy is relatively new, only about 20 - 30 years old, but has gained wide use. In some pediatric departments up to 10% of the newborns are treated. It is an excellent mode of therapy and should be used when indicated. However, its use should be optimized; like ionizing radiation therapy it possesses demonstrated risks, particularly risks of genotoxicity. Factors such as light dose and light wavelength should be controlled with this purpose, and the parameters should be registered in order to facilitate future follow-up studies.
1 T. Christensen, Cytotoxicity of bilirubin photoproducts, Photobiochem. Photobiophys., 10 (1986) 253 - 260. 2 T. Christensen, A. St&turn, G. Brunborg and J. B. Reitan, Unwanted side effects and optimization of phototherapy, F’roc. 2nd Meet. of the ESP, Plenum, to be published. 3 B. S. Rosenstein, J. M. Ducore and S. W. Cummings, The mechanism of bilirubinphotosensitized DNA strand breakage in human cells exposed to phototherapy light, Mutat. Res., 112 (1983) 397 - 406. 4 C. Vecchi, G. P. Donzelli, M. G. Migliorini, G. Serana and R. Pratesi, New light in phototherapy, Lancet, (August 14,1982) 390.
373
Instruments that measure IR luminescence during continuous illumination operate on the time integral of eqn. (1) which leads to L = b’k,T*&&
(1 -
lo-Ax)
wave (4)
from which we see that TA influences the observed signal amplitude and, as above, conditions that decrease rA will adversely affect the signal. As stated above, most red-light-absorbing sensitizers have weak, but significant, fluorescence intensity in the spectral region where O,( ‘Ag) emits. Thus luminescence spectral measurements invariably show the singlet oxygen peak sitting atop a significant background. As rA decreases the 1.27 pm peak tends to disappear into this background and be indistinguishable therefrom. One possibility for picking out the (presumably) longer-lived singlet oxygen emission is to use a phase-sensitive detection system and frequencymodulated illumination. In this way rapidly decaying fluorescence can be separated from slower-decaying luminescence by taking advantage of the resulting phase differences. Such a method has been described and used [2 ] for demonstrating 1.27 pm luminescence from red-light-illuminated, porphyrin-containing tissue samples. As with the other techniques, the phase modulation method suffers progressively as rA shortens owing to quenching processes. Of course, given optimum sensitivity and observational bandwidth it would be surprising if the combination of light, sensitizer and oxygen did not produce singlet oxygen. The next generation of experiments must attempt to quantify O,( ‘As) yields and correlate them with damage to tissue, cell death, and effects at the organelle level. For these demands to be effectively carried out, a new generation of instruments having high sensitivity at higher bandwidth needs to be developed. 1 M. A. J. Rodgers, Singlet oxygen quantum yields. In J. R. Heitz and K. R. Downum (eds.), Light Activated Pesticides, A. C. S. Symp. Ser. 339, Washington, DC, 1987, pp. 76 - 97. 2 J. G. Parker, Optical monitoring of singlet oxygen generation during photodynamic treatment of tumors, IEEE Circuits and Deuices Magazine, (January, 1987) 10 - 21.
Phototoxic
effects of bilirubin
T. CHRISTENSEN Medical Section, (Norway)
and J. B. REITAN National Znstitute
Phototherapy safe and efficient
of Radiation
Hygiene,
P.O. Box 55, N-1345
OsterBs
of neonatal jaundice is widely used and is regarded as a way of reducing the bilirubin concentration in different
374
NEWS AND VIEWS
tissues. The bilirubin is able to participate in a number of photochemical reactions. Some of them lead to the facilitated excretion of bilirubin, but it has recently been shown that some may also be potentially harmful to the infant [ 1 - 31. The exact mechanism behind the therapeutic effect has been debated, but today there is a general agreement that photoisomerization of bilirubin is the main photochemical mechanism for converting bilirubin to a more water-soluble and excretable form. Isomerizations to geometric and structural isomers are the most quantum-efficient processes, but photo-oxidation may take place as well. Under particular conditions in vitro cytotoxic photoproducts are formed. These are quite long lived and can cause cell death accompanied by single-strand breaks in the DNA and mutations in hamster cells. Of course such biological effects cause some worry about the safety of phototherapy. However, at the moment the deleterious effects seen in cell cultures have only been looked for in a limited number of cell types and under particular culture conditions. An open question is for example why the effects seem only to be produced in media containing calf serum or in the absence of serum, and not in human serum. If it is accepted that oxidation products formed by self-sensitized photo-oxidation of bilirubin are responsible for the toxic effects in vitro, the mode of binding of bilirubin in different tissues is important. None of the toxic effects are observed in the presence of human serum, and therefore bilirubin in the blood circulation seems not to represent a risk. Too little is known about how bilirubin is bound in other tissues. The phototoxic effects have been shown using blue light. Other wavelengths such as green light will be tested. From general experience with light effects, it can be assumed that green light may be safer and it has been shown that it may even be effective in therapy [ 41. Phototherapy is relatively new, only about 20 - 30 years old, but has gained wide use. In some pediatric departments up to 10% of the newborns are treated. It is an excellent mode of therapy and should be used when indicated. However, its use should be optimized; like ionizing radiation therapy it possesses demonstrated risks, particularly risks of genotoxicity. Factors such as light dose and light wavelength should be controlled with this purpose, and the parameters should be registered in order to facilitate future follow-up studies.
1 T. Christensen, Cytotoxicity of bilirubin photoproducts, Photobiochem. Photobiophys., 10 (1986) 253 - 260. 2 T. Christensen, A. St&turn, G. Brunborg and J. B. Reitan, Unwanted side effects and optimization of phototherapy, F’roc. 2nd Meet. of the ESP, Plenum, to be published. 3 B. S. Rosenstein, J. M. Ducore and S. W. Cummings, The mechanism of bilirubinphotosensitized DNA strand breakage in human cells exposed to phototherapy light, Mutat. Res., 112 (1983) 397 - 406. 4 C. Vecchi, G. P. Donzelli, M. G. Migliorini, G. Serana and R. Pratesi, New light in phototherapy, Lancet, (August 14,1982) 390.