Browsing by Subject "Ultraviolet radiation"

Now showing 1 - 7 of 7
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    Cumulative Erythemal Ultraviolet Radiation and Risk of Cancer in 3 Large US Prospective Cohorts
    (Oxford University Press, 2022) Chang, Michael S.; Hartman, Rebecca I.; Trepanowski, Nicole; Giovannucci, Edward L.; Nan, Hongmei; Li, Xin; Epidemiology, School of Public Health
    Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and noncutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined 3 US prospective cohorts, the Health Professionals Follow-up Study (HPFS) (1986) and Nurses’ Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding nonmelanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 men; 212,449 women) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as referent, for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared with the lowest quintile, risk of any cancer was slightly increased across all other quintiles (highest quintile hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.01, 1.07; P for heterogeneity = 0.41). All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR = 1.17, 95% CI: 1.04, 1.31; P for heterogeneity = 0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and noncutaneous cancers.
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    Estrogen receptor involvement in the response of human keratinocytes to ultraviolet B irradiation
    (2014) Farrington, Daphne L.; Spandau, Dan F.; Harrington, Maureen A.; Nakshatri, Harikrishna
    The signaling mechanisms involved in UVB-induced skin cancer are complex and although the scope of this work is inherently limited in focus, the findings may provide insight into how estrogen receptor signaling impacts cell growth, senescence, and apoptosis to protect keratinocytes. Additional signaling due to E2-activation of the estrogen receptor may provide back-up or redundant pathways in response to UVB.
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    Exploring the mechanism of action of spore photoproduct lyase
    (2014-08-27) Nelson, Renae; Li, Lei; Long, Eric C. (Eric Charles); McLeish, Michael J.
    Spore photoproduct lyase (SPL) is a radical SAM (S-adenosylmethionine) enzyme that is responsible for the repair of the DNA UV damage product 5-thyminyl-5,6-dihydrothymine (also called spore photoproduct, SP) in the early germination phase of bacterial endospores. SPL initiates the SP repair process using 5'-dA• (5'-deoxyadenosyl radical) generated by SAM cleavage to abstract the H6proR atom which results in a thymine allylic radical. These studies provide strong evidence that the TpT radical likely receives an H atom from an intrinsic H atom donor, C141 in B. subtilis SPL. I have shown that C141 can be alkylated in native SPL by iodoacetamide treatment indicating that it is accessible to the TpT radical. Activity studies demonstrate a 3-fold slower repair rate of SP by C141A which produces TpTSO2 - and TpT simultaneously with no lag phase observed for TpTSO2- formation. Additionally, formation of both products shows a Dvmax kinetic isotope effect (KIE) of 1.7 ± 0.2 which is smaller than the DVmax KIE of 2.8 ± 0.3 for the WT SPL reaction. Removal of the intrinsic H atom donor by this single mutation disrupts the rate-limiting process in the enzyme catalysis. Moreover, C141A exhibits ~0.4 turnover compared to the > 5 turnovers in the WT SPL reaction. In Y97 and Y99 studies, structural and biochemical data suggest that these two tyrosine residues are also crucial in enzyme catalysis. It is suggested that Y99 in B. subtilis SPL uses a novel hydrogen atom transfer pathway utilizing a pair of cysteinetyrosine residues to regenerate SAM. The second tyrosine, Y97, structurally assists in SAM binding and may also contribute to SAM regeneration by interacting with radical intermediates to lower the energy barrier for the second H-abstraction step.
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    Recreational and residential sun exposure and risk of endometriosis: a prospective cohort study
    (Oxford University Press, 2021) Farland, Leslie V.; Degnan, William J.; Harris, Holly R.; Han, Jiali; Cho, Eunyoung; VoPham, Trang; Kvaskoff, Marina; Missmer, Stacey A.; Epidemiology, School of Public Health
    Study question: Is recreational and residential sun exposure associated with risk of endometriosis? Summary answer: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk. What is known already: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk. Study design, size, duration: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015. Participants/materials, settings, methods: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs. Main results and the role of chance: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252 248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis. Limitations, reasons for caution: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records. Wider implications of the findings: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology.
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    Step-growth thiol-ene photopolymerization to form degradable, cytocompatible and multi-structural hydrogels
    (2014-01-17) Shih, Han; Lin, Chien-Chi; Xie, Dong; Bottino, Marco
    Hydrogels prepared from photopolymerization have been used for a variety of tissue engineering and controlled release applications. Polymeric biomaterials with high cytocompatibility, versatile degradation behaviors, and diverse material properties are particularly useful in studying cell fate processes. In recent years, step-growth thiol-ene photochemistry has been utilized to form cytocompatible hydrogels for tissue engineering applications. This radical-mediated gelation scheme utilizes norbornene functionalized multi-arm poly(ethylene glycol) (PEGNB) as the macromer and di-thiol containing molecules as the crosslinkers to form chemically crosslinked hydrogels. While the gelation mechanism was well-described in the literature, the network properties and degradation behaviors of these hydrogels have not been fully characterized. In addition, existing thiol-ene photopolymerizations often used type I photoinitiators in conjunction with an ultraviolet (UV) light source to initiate gelation. The use of cleavage type initiators and UV light often raises biosafety concerns. The first objective of this thesis was to understand the gelation and degradation properties of thiol-ene hydrogels. In this regard, two types of step-growth hydrogels were compared, namely thiol-ene hydrogels and Michael-type addition hydrogels. Between these two step-growth gel systems, it was found that thiol-ene click reactions formed hydrogels with higher crosslinking efficiency. However, thiol-ene hydrogels still contained significant network non-ideality, demonstrated by a high dependency of hydrogel swelling on macromer contents. In addition, the presence of ester bonds within the PEGNB macromer rendered thiol-ene hydrogels hydrolytically degradable. Through validating model predictions with experimental results, it was found that the hydrolytic degradation of thiol-ene hydrogels was not only governed by ester bond hydrolysis, but also affected by the degree of network crosslinking. In an attempt to manipulate network crosslinking and degradation rate of thiol-ene hydrogels, different macromer contents and peptide crosslinkers with different amino acid sequences were used. A chymotrypsin-sensitive peptide was also used as part of the hydrogel crosslinkers to render thiol-ene hydrogels enzymatically degradable. The second objective of this thesis was to develop a visible light-mediated thiol-ene hydrogelation scheme using a type II photoinitiator, eosin-Y, as the only photoinitiator. This approach eliminates the incorporation of potentially cytotoxic co-initiator and co-monomer that are typically used with a type II initiator. In addition to investigating the gelation kinetics and properties of thiol-ene hydrogels formed by this new gelation scheme, it was found that the visible light-mediated thiol-ene hydrogels were highly cytocompatible for human mesenchymal stem cells (hMSCs) and pancreatic MIN6 beta-cells. It was also found that eosin-Y could be repeatedly excited for preparing step-growth hydrogels with multilayer structures. This new gelation chemistry may have great utilities in controlled release of multiple sensitive growth factors and encapsulation of multiple cell types for tissue regeneration.