Induction and Excretion of Ultraviolet-Induced 8-Oxo-2′-deoxyguanosine and Thymine Dimers In Vivo: Implications for PUVA

Cooke, Marcus S.; Evans, Mark D.; Burd, Robert M.; Patel, Kalpana; Barnard, A.; Lunec, Joseph; Hutchinson, P.E.

doi:10.1046/j.1523-1747.2001.01251.x

Cited by 57 publications

(38 citation statements)

References 54 publications

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“…The data for each day are expressed as a percentage of the total amount of T = T and compared statistically (t test) with day 3 (*, P < 0.05; **, P < 0.01; ***, P < 0.001). analyzed using an immunologic method (15,16). The results showed that T = T peaked at day 3 (15), which is consistent with our data.…”

Section: Discussionsupporting

confidence: 91%

“…analyzed using an immunologic method (15,16). The results showed that T = T peaked at day 3 (15), which is consistent with our data. However, the increase in T = T levels from the prestudy levels was much less in the reported study compared with ours.…”

Section: Discussionsupporting

confidence: 91%

“…However, the increase in T = T levels from the prestudy levels was much less in the reported study compared with ours. The spectra of the lamps used in the two studies were very similar and the erythema-weighted dose of 383 J/m 2 used by us corresponds to an unweighted dose of 17 J/cm 2 , i.e., very close to the 15 J/cm 2 used by Cooke et al (15). The reasons for the discrepancies between the two studies are therefore unknown, but they could be due to differences in the assays used for T = T analysis.…”

Section: Discussionsupporting

confidence: 76%

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Urinary Thymidine Dimer as a Marker of Total Body Burden of UV-Inflicted DNA Damage in Humans

Kotova

Hemminki²,

Segerbäck

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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High levels of DNA damage are induced in human skin following exposure to UV radiation. Cyclobutane thymidine dimer (T = T) is the most common of these lesions, which are enzymatically removed as oligonucleotides from DNA and further degraded before excretion in urine. Analysis of such repair products in the urine could serve as a biomarker of total body burden of UV exposure. The aim of this study was to examine the kinetics of T = T excretion following a single tanning session in a commercial solarium and to validate the method by delivering different doses. Ten individuals used the solarium for a total of 35 sessions of body tanning. Urine was collected before UV exposure and daily thereafter (up to 5 or 11 days) and T = T was analyzed using a very sensitive and quantitative 32 P-postlabeling technique combined with high-performance liquid chromatography. Following exposure, T = T levels increased dramatically and reached a peak 3 days later; afterwards, the T = T levels gradually decreased. The total amount of T = T excreted differed about 5-fold among subjects given an equal dose. A 50% excretion time was calculated using the excretion data for the first 5 days and it was found to be between 55 and 76 hours for different individuals. There was a good correlation between the amount of T = T excreted during days 1 to 5 and the delivered UV dose. Reducing exposure time to 50% lowered the amount of T = T to 47%; if half of the lamps were covered, T = T decreased to 44%. Our data show that urinary T = T could be a suitable noninvasive biomarker for UV exposure; a finding which could also be applicable to studies in children. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2868 -72)

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 76%

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Urinary Thymidine Dimer as a Marker of Total Body Burden of UV-Inflicted DNA Damage in Humans

Kotova

Hemminki²,

Segerbäck

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The oxidized product of DNA, 8-hydroxy-2'-deoxyguanosine , is the most frequently measured biomarker of the oxidative stress [7,8]. The 8-OHdG has been analyzed in various kinds of samples, such as urine, serum, peripheral blood leukocyte, and organ tissue [9].…”

Section: Introductionmentioning

confidence: 99%

Analysis of 8-hydroxy-2′-deoxyguanosine in human urine using hydrophilic interaction chromatography with tandem mass spectrometry

Hosozumi

Toriba

Chuesaard

et al. 2012

Journal of Chromatography B

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Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a widely used noninvasive biomarker of oxidative stress. A selective, sensitive and rapid method for determining 8-OHdG in human urine was developed using hydrophilic interaction chromatographytandem mass spectrometry (HILIC-MS/MS) with electrospray ionization. 8-OHdG and isotopically labeled 8-OHdG (internal standard) were separated on a HILIC column with a mobile phase of 10 mM ammonium acetate : acetonitrile (1 : 9, v/v) within 10 min and detected by using a positive electrospray ionization interface under the selected reaction monitoring mode. The detection limits of 8-OHdG (corresponding to a signal-to-noise ratio of 3) for the HILIC-MS/MS system and the conventional method using a reversed-phase column with MS/MS were 1.0 and 26.0 fmol/injection, respectively. The proposed method makes it possible to monitor the basal level of urinary 8-OHdG from non-exposed healthy subjects and can be used for large-scale human studies.

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“…As the increase of oxidative stress may lead to oxidative DNA damage, we also measured the level of 8-hydroxy-2′-deoxyguanosine (8-OXO-dG), a marker of oxidative DNA damage, 17 in the liver of L-Atg5-KO mice. Indeed, as shown in Figure 2e, the 8-OXO-dG level was significantly higher in the liver of L-Atg5-KO mice than in the spleen of these mice or the liver of control mice at 2 and 4 months of age.…”

mentioning

confidence: 99%

Autophagy inhibits oxidative stress and tumor suppressors to exert its dual effect on hepatocarcinogenesis

et al. 2014

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The role of autophagy in carcinogenesis is controversial and apparently complex. By using mice with hepatocyte-specific knockout of Atg5, a gene essential for autophagy, we longitudinally studied the role of autophagy in hepatocarcinogenesis. We found that impairing autophagy in hepatocytes would induce oxidative stress and DNA damage, followed by the initiation of hepatocarcinogenesis, which could be suppressed by the antioxidant N-acetylcysteine. Interestingly, these mice developed only benign tumors with no hepatocellular carcinoma (HCC), even after the treatment with diethylnitrosamine, which induced HCC in wild-type mice. The inability of mice to develop HCC when autophagy was impaired was associated with the induction of multiple tumor suppressors including p53. Further analysis indicated that the induction of p53 was associated with the DNA-damage response. Tumorigenesis studies using an established liver tumor cell line confirmed a positive role of autophagy in tumorigenesis and a negative role of p53 in this process when autophagy was impaired. Our studies thus demonstrate that autophagy is required to maintain healthy mitochondria and to reduce oxidative stress and DNA damage to prevent the initiation of hepatocarcinogenesis. However, once hepatocarcinogenesis has been initiated, its presence is also required to suppress the expression of tumor suppressors to promote the development of HCC. Autophagy (i.e., macroautophagy) is important for cells to remove protein aggregates and damaged organelles. Its dysfunction can cause a variety of diseases including cancers. 1,2 However, its role in carcinogenesis is apparently complex, as it has been shown in different reports to positively or negatively regulate carcinogenesis. 3,4 Autophagy apparently can function as a tumor suppressor, as the gene encoding Beclin-1, a component of the phosphatidylinositol-3-kinase class III (PI3KC3) complex that is essential for the initiation of autophagy, is often monoallelically deleted or mutated in breast, ovarian and prostate cancers. 5 Frameshift mutations in Atg2B, Atg5, Atg9B and Atg12 autophagy genes are also often found in gastric and colorectal cancers with microsatellite instability. 6 The tumor suppressor role of autophagy is further supported by the studies using mouse models. It has been shown that the monoallelic deletion of the Beclin-1 gene in mice induced tumor lesions in various tissues, 7 Atg4C-knockout (KO) mice had increased susceptibility to carcinogens for the development of fibrosarcomas 8 and the systemic mosaic KO of Atg5 and the liver-specific KO of Atg7 in mice led to the development of benign liver adenomas. 9,10 Autophagy has also been shown to promote tumor growth. It has been shown that autophagy can enhance the survival of tumor cells in the hypoxic regions of solid tumors. 11 It has also been shown that in cells expressing oncogenic Ras, autophagy is required to promote tumorigenesis by maintaining oxidative metabolism or facilitating glycolysis. 12,13 Moreover, it has also been demonstrate...

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Induction and Excretion of Ultraviolet-Induced 8-Oxo-2′-deoxyguanosine and Thymine Dimers In Vivo: Implications for PUVA

Cited by 57 publications

References 54 publications

Urinary Thymidine Dimer as a Marker of Total Body Burden of UV-Inflicted DNA Damage in Humans

Urinary Thymidine Dimer as a Marker of Total Body Burden of UV-Inflicted DNA Damage in Humans

Analysis of 8-hydroxy-2′-deoxyguanosine in human urine using hydrophilic interaction chromatography with tandem mass spectrometry

Autophagy inhibits oxidative stress and tumor suppressors to exert its dual effect on hepatocarcinogenesis

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