A Spectrum Response Study on Single Strand DNA Breaks, Sister Chromatid Exchanges, and Lethality Induced by Phototherapy Lights

Sideris, E.G.; Papageorgiou, George C.; Charalampous, Sylva C; Vitsa, E.

doi:10.1203/00006450-198107000-00008

Cited by 44 publications

(30 citation statements)

References 23 publications

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“…Light from standard fluorescent lamps causes breaks in DNA strands in vitro (3, 35) and increases sister chromatid exchanges and other chromosomal alterations in cultured cells (4,18,21,23,32,35,37). An increased frequency of sister chromatid exchange has been reported in some infants after phototherapy (12).…”

Section: Discussionmentioning

confidence: 99%

“…Although we know of no reports regarding any increase in sister chromatid exchange in vivo in response to monochromatic light, the occurrence seems likely; thus, the widespread use of phototherapy has generated concern regarding the potential for long-term mutagenic and carcinogenic effects. Inasmuch as most published data suggest that the offending wavelengths are principally in the ultraviolet range, some recent work has implicated light of wavelengths exceeding 300 nm (9) and, indeed, some alterations appear to occur maximally in response to wavelengths of light between 420-500 nrn (35). Although the magnitude of these latter risks has not been quantitated as they may relate to the clinical setting, it seems desirable to more precisely define the most efficacious wavelengths for the photoalteration of bilirubin that results in its enhanced excretion.…”

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confidence: 99%

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The in Vitro and in Vivo Photoreactivity of Bilirubin: I. Laser-Defined Wavelength Dependence

1983

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SummaryMonochromatic light was provided by a continuous wave Argon ion laser. We chose to study the in vitro effects of light at 457.9, 465.8, 476.5, 488.0, 501.7, and 514.5 nm as representative of a reasonably evenly spaced samplig across the blue-green spectrum. The in vivo experiments were conducted at 457.9, 476.5, 488.0, and 514.5 nm.In vitro light at 488.0 nm appeared to be more effective than the others studied.After 24 h of irradiance, the in vivo decline in serum bilirubin concentration produced by light at 488.0 nm was one-and-one-half, two, and four times as effective as light at 457.9, 476.5 and 514.5 nm, respectively. By 48 h of exposure, the declines produced by light at 457.9 nm and 488.0 nm are significantly superior to that at 476.5 nm and 514.5 nm, but they do not differ from one another.The photon-induced chemical alteration of bilirubin has been demonstrated by various light sources both in vitro and in vivo. The clinical application of this phenomenon has been widely used as phototherapy in the treatment of neonatal hyperbilirubinemia. Investigations designed to delineate the effective wavelengths have employed broad spectrum light sources and have indicated that irradiance with light of wavelengths of 425-475 nm is maximally effective both in vitro (2,7,8,10, 13,25,31) and in vivo (1,11,17,24,29,33,36). But one study performed in vitro with a relatively narrow spectral source suggested wavelengths at 490 nm might also be efficacious (10). More recently, Lilien et al. (27) have performed experiments that also suggest that wavelengths of light beyond the 425475 nm range are efficacious in vitro.Radiant energies within the 400-500 nm range exhibit potential for inducing damage to tissues. Light from standard fluorescent lamps causes breaks in DNA strands in vitro (3, 35) and increases sister chromatid exchanges and other chromosomal alterations in cultured cells (4,18,21,23,32,35,37). An increased frequency of sister chromatid exchange has been reported in some infants after phototherapy (12). Although we know of no reports regarding any increase in sister chromatid exchange in vivo in response to monochromatic light, the occurrence seems likely; thus, the widespread use of phototherapy has generated concern regarding the potential for long-term mutagenic and carcinogenic effects. Inasmuch as most published data suggest that the offending wavelengths are principally in the ultraviolet range, some recent work has implicated light of wavelengths exceeding 300 nm (9) and, indeed, some alterations appear to occur maximally in response to wavelengths of light between 420-500 nrn (35). Although the magnitude of these latter risks has not been quantitated as they may relate to the clinical setting, it seems desirable to more precisely define the most efficacious wavelengths for the photoalteration of bilirubin that results in its enhanced excretion. This is particularly needed in the design of future phototherapy instruments to be used in the management of neonatal hyperbilirubinemia. Preliminary po...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The in Vitro and in Vivo Photoreactivity of Bilirubin: I. Laser-Defined Wavelength Dependence

1983

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“…Such concerns seem justified in view of DNA modifying activity of phototherapy (9), a property shared with many chemical carcinogens and teratogens (1). The photodynamic damage of intracellular DNA has been well characterized and is enhanced by, but not dependent upon, the presence of exogenous photosensitizing agents (3,7,10,11). Such enhancement takes on clinical significance when it is realized that many low birth-weight infants receiving phototherapy are simultaneously administered parenteral hyperalimentation solutions containing photosensitizers, i.e., multivitamins, amino acids, etc.…”

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confidence: 99%

Potential for Genetic Damage from Multivitamin Solutions Exposed to Phototherapy Illumination

1983

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Summarysubsequently washed with PBS and each flask supplemented withThe ability of standard phototherapy illumination to produce damage in intracellular DNA is well established. In this study, the addition of a dilute solution (1:6400) of a clinically-used multivitamin concentrate to human KB cells was found to enhance the generation of single-strand DNA breaks produced by broad-spectrum fluorescent light. The effect of the exogenous photosensitizing agent (multivitamins) was blocked by the enzyme catalase; thus, the photoproduct responsible for the DNA modification was hydrogen peroxide, an extremely reactive molecule capable of damaging a variety of biologic macromolecules. Abbreviations PBS, phosphate buffered saline DSPBS, 5% (w/v) dextrose in phosphate buffered saline

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“…Since the introduction of phototherapy, serious long-term effects have not been reported. However, there have been reports of phototherapy-induced DNA damage to human cell lines in vitro and bilirubin was found to enhance this damage (7,8).…”

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confidence: 99%

Novel Kinetic Insights into Treatment of Unconjugated Hyperbilirubinemia: Phototherapy and Orlistat Treatment in Gunn Rats

et al. 2006

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ABSTRACT:Treatment with phototherapy or with the lipase inhibitor orlistat decreases plasma unconjugated bilirubin (UCB) concentrations in hyperbilirubinemic Gunn rats. We investigated the mechanism(s) underlying the effects of orlistat, phototherapy, and combined treatment, using steady-state 3 H-UCB kinetics. After three weeks of treatment with orlistat (200 mg/kg chow), phototherapy (19 W/cm 2 /nm) or combined treatment, tracer 3 H-UCB was administered IV to treated and untreated (control) Gunn rats. Plasma samples and feces were collected every 12h for 60h, and bile for 30 min at 60h. The following results were obtained: 1) each treatment decreased plasma bilirubin levels compared with controls: orlistat-19%, phototherapy-32%, combined treatment-53%; 2) plasma bilirubin concentrations were strongly, negatively correlated with fractional bilirubin turnover; 3) orlistat treatment induced net transmucosal excretion of UCB into the intestinal lumen, whereas phototherapy increased biliary UCB excretion rate; 4) all treatments profoundly increased the enterohepatic circulation of UCB derivatives, indicating enhanced metabolism by intestinal bacteria. In conclusion, orlistat and phototherapy lower plasma bilirubin concentrations in Gunn rats by increasing (net) intestinal influx of UCB, either by transmucosal excretion (orlistat), or increased biliary secretion (phototherapy). The mechanism of phototherapy and orlistat treatment involves increasing the availability of UCB in the intestinal lumen for fecal excretion and for metabolism by intestinal bacteria.

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A Spectrum Response Study on Single Strand DNA Breaks, Sister Chromatid Exchanges, and Lethality Induced by Phototherapy Lights

Cited by 44 publications

References 23 publications

The in Vitro and in Vivo Photoreactivity of Bilirubin: I. Laser-Defined Wavelength Dependence

The in Vitro and in Vivo Photoreactivity of Bilirubin: I. Laser-Defined Wavelength Dependence

Potential for Genetic Damage from Multivitamin Solutions Exposed to Phototherapy Illumination

Novel Kinetic Insights into Treatment of Unconjugated Hyperbilirubinemia: Phototherapy and Orlistat Treatment in Gunn Rats

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