The mechanism of bilirubin-photosensitized DNA strand breakage in human cells exposed to phototherapy light

Rosenstein, Barry S.; Ducore, Jonathan M.; Cummings, Scott W.

doi:10.1016/0167-8817(83)90032-9

Cited by 41 publications

(39 citation statements)

References 16 publications

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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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confidence: 99%

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

et al. 2006

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“…Ultraviolet light, which is a form of visible light, and phototherapy light have been shown to damage DNA in vitro and in vivo [37][38][39][40][41][42]. However, some studies reported that phototherapy light has no significant impact on nuclear material [43,44].…”

Section: Discussionmentioning

confidence: 99%

Once the Light Touch to the Brain: Cytotoxic Effects of Low-Dose Gamma-Ray, Laser Light, and Visible Light on Rat Neuronal Cell Culture

et al. 2016

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Objective: We aimed to evaluate the effects of gamma-ray, laser light, and visible light, which neurons are commonly exposed to during treatment of various cranial diseases, on the viability of neurons. Materials and Methods:Neuronal cell culture was prepared from the frontal cortex of 9 newborn rats. Cultured cells were irradiated with gamma-ray for 1-10 min by 152 Eu, 241 Am, and 132 Ba isotopes, visible light for 1-160 min, and laser light for 0.2-2 seconds. The MTT tetrazolium reduction assay was used to assess the number of viable cells in the neuronal cell cultures. Wavelength dispersive X-ray fluorescence spectrometer was used to determine Na, K, and Ca levels in cellular fluid obtained from neuronal cell culture plaques. Ba isotopes, cell viability insignificantly decreased with time (p>0.05). On the other hand, exposure to visible light produced statistically significant decrease in cell viability at both short-(1-10 min) and long-term (20-160 min). Cell viability did not change with 2 seconds of laser exposure. Na, K, and Ca levels significantly decreased with gamma-ray and visible light. The level of oxidative stress markers significantly changed with gamma-ray. Results Conclusion:In conclusion, while low dose gamma-ray has slight to moderate apoptotic effect in neuronal cell cultures by oxidative stress, long-term visible light induces remarkable apoptosis and cell death. Laser light has no significant effect on neurons. Further genetic studies are needed to clarify the chronic effect of visible light on neuronal development and functions.Keywords: Neuron, cytotoxicity, cell culture, apoptosis, laser light, radiation Öz Amaç: Amacımız, çeşitli kranial hastalıkların tedavisi esnasında nöronların sıklıkla maruz kaldığı gama ışını, laser ışığı ve görünür ışığın etkilerinin değerlendirilmesidir. Ba izotoplar ile düşük dozda radyasyon altında, istatiksel olarak anlamsız bir, zamanla azaldı. Öte yandan, görünür ışığa maruziyet hücre canlılığında hem kısa süreli (1-10 dk) hem de uzun süreli (20-160 dk) maruziyette anlamlı derecede düşüşe sebep olur. Hücre canlılığı lazere 2 saniye maruz kalma ile değişmedi. Na, K ve Ca seviyeleri gama ışını ve görünür ışık maruziyeti ile önemli ölçüde azalmıştır. Oksidatif stres belirteçleri seviyesi gama-ışını ile önemli ölçüde değişti. Gereç veSonuç: Düşük doz gama ışını oksidatif strese bağlı nöronal hücre kültürlerindeki apoptotik etkisi hafif ve orta düzeydeyken, uzun sü-reli görünür ışık dikkate değer bir apoptoz ve hücre ölümüne neden oldu. Lazer ışığı nöronlar üzerinde önemli bir etkiye sahip değildir. Görünür ışığın nöron gelişimi ve işlevleri üzerinde kronik etkisini açıklamak için ileri genetik çalışmalar yapılmasına ihtiyaç vardır.

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“…Although phototherapy has some known adverse effects including skin rash, diarrhea, dehydration, and oxidative stress, no other method with fewer adverse effects that can be used conveniently has yet been developed for the treatment of hyperbilirubinemia (1,2). In addition to the above-mentioned adverse effects, it has been shown that phototherapy might also have adverse effects on chromosomes in some animal and clinical studies (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

The effect of phototherapy on sister chromatid exchange with different light density in newborn hyperbilirubinemia

Kanmaz¹,

Okur²,

Díllí³

et al. 2018

Turk Pediatri Ars

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Aim: Concerns of possible genotoxic effects of hyperbilirubinemia and phototherapy were raised from experimental and observational studies in neonates. The purpose of this study was to assess the effect of hyperbilirubinemia and phototherapy with three different methods on DNA damage by investigating sister chromatid exchange frequency. Material and Methods: Patients whose gestational ages were >37 weeks and bilirubin levels above phototherapy limits were enrolled into three groups and each group was planned to receive 25 babies. Group 1 received enhanced light-emitting diode phototherapy, group 2 had light-emitting diode phototherapy, and group 3 received conventional phototherapy. Infants with hyperbilirubinemia but did not require phototherapy comprised the control group, which was subdivided into two groups regarding bilirubin levels (10mg/dL). Blood samples were collected before and after phototherapy for sister chromatid exchange frequency and samples were examined by a biologist who was blinded to the study groups. Results: The mean pre-treatment sister chromatid exchange frequency was 1.41±0.34/cell, post-treatment 2.65±0.68/cell, and 1.61±0.61/ cell for the control group (p<0.05). A statistically significant increase in sister chromatid exchange frequency after phototherapy was observed in all three intervention groups (p values: 0.01, 0.01, and 0.008, respectively). When the treatment groups were compared with each other in terms of irradiance, no significant difference was found (p=0.08). Conclusions: Phototherapy causes an increase in the frequency of sister chromatid exchange regardless of the irradiance. Phototherapy could have some genotoxic adverse effects on chromosomes; however, further investigations are warranted to enlighten as to whether these effects are permanent or clinically important.

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The mechanism of bilirubin-photosensitized DNA strand breakage in human cells exposed to phototherapy light

Cited by 41 publications

References 16 publications

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

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

Once the Light Touch to the Brain: Cytotoxic Effects of Low-Dose Gamma-Ray, Laser Light, and Visible Light on Rat Neuronal Cell Culture

The effect of phototherapy on sister chromatid exchange with different light density in newborn hyperbilirubinemia

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