Holiday sun exposure increases level of vitamin D and thymine dimmers in children

Wstęp: Ekspozycja na słońce powoduje syntezę witaminy D, która odgrywa istotną rolę w wielu procesach zachodzących w organizmie człowieka. Celem pracy było ustalenie wpływu UVR na syntezę witaminy D oraz uszkodzenie DNA w populacji dzieci w wieku szkolnym w odniesieniu do indywidualnej dawki promieniowania. Materiał i metody: Badanie przeprowadzono w okresie wakacyjnym na grupie 32 dzieci rasy kaukaskiej podczas 2-tygodniowego pobytu nad Morzem Bałtyckim. Od wszystkich ochotników pobrano próbki krwi w celu pomiaru stężenia witaminy D, parathormonu, cross-laps, osteokalcyny i moczu w celu analizy uszkodzenia DNA na podstawie oceny stężenia dimerów tymidynowych (T = T). Pomiarów dokonano 24 godziny przed wyjazdem oraz 24 godziny po powrocie z wakacji. Wyniki: Analiza statystyczna wykazała znaczne różnice w wartościach PPF zmierzonych na czole oraz wartościach PPF i pigmentacji mierzonych na ramionach i przedramionach. Wykazano dodatnią korelację pomiędzy PPF zmierzonym na czole a zmianą stężenia 25(OH) D. Mediana stężenia 25(OH)D po powrocie z obozu wzrosła istotnie w stosunku do poziomu wyjściowego. Stężenie PTH (parathormonu), osteokalcyny oraz cross-laps nie zmieniło się istotnie statystycznie po ekspozycji na promieniowanie słoneczne. Stężenie dimerów tymidynowych wzrosło znamiennie statystycznie po ekspozycji na słońce, uzyskując wyższe wartości wśród dzieci z I/II fototypem skory. Nie wykazano korelacji pomiędzy stężeniem T = T a stężeniem witaminy D w surowicy. Wnioski: Uzyskane wyniki wskazują zarówno korzystne, jak i szkodliwe działanie ekspozycji słonecznej na zdrowie dzieci. Zwiększenie poziomu witaminy D i z drugiej strony wzrost w syntezie T = T są niejednoznaczne w interpretacji. Dlatego wciąż aktualne wydaje się prowadzenie badań dotyczących indywidualnej ekspozycji na promieniowanie słoneczne, ochrony przeciwsłonecznej oraz suplementacji witaminą D.Introduction: Sun exposure involves to synthesis of vitamin D, which is associated with many processes in the human body. The aim of the study was to determine the effect of UVR on the synthesis of vitamin D and DNA damage in the population of children including the individual radiation dose. Material and methods: The study was conducted on a group of 32 children during 2-week stay by the Baltic Sea. Blood samples were taken to measure levels of vitamin D, PTH, cross-laps and osteocalcin, and urine samples for analysis of DNA damage based on the concentration of thymidine dimers (T = T). Measurements were performed 24 hours before and 24 hours after returning. Statistical analysis revealed significant difference in PPF values measured on forehead and on upper and lower arm. Results: Positive correlation between PPF on the forehead and change (Δ) 25(OH)D was founded. Median value of 25(OH)D after camp increased statistically comparing to baseline level. Levels of PTH, osteocalcine and cross-laps didn’t differ significantly after sun exposure. T = T levels increased statistically significant after esposure and higher values was obtained among the children with I/II phototype. Statistical analysis gave no significant correlations between T = T levels and vitamin D concentration. Conclusions: The results show both beneficial and harmful effects of natural sun exposure on children’s health. Increase of vitamin D levels and on the other hand increase in T = T synthesis are confusing to be interpreted. Therefore, it still seems to be valid to conduct research involved individual exposure to sunlight, UVR protection and supplementation of vitamin D

PRIMA-1 reactivates mutant p53 by covalent binding to the core domain

Restoration of wild-type p53 expression triggers cell death and eliminates tumors in vivo. The identification of mutant p53-reactivating small molecules such as PRIMA-1 opens possibilities for the development of more efficient anticancer drugs. Although the biological effects of PRIMA-1 are well demonstrated, little is known about its molecular mechanism of action. We show here that PRIMA-1 is converted to compounds that form adducts with thiols in mutant p53. Covalent modification of mutant p53 per se is sufficient to induce apoptosis in tumor cells. These findings might facilitate the design of more potent and specific mutant p53-targeting anticancer drugs

Sun and Ski Holidays Improve Vitamin D Status, but Are Associated with High Levels of DNA Damage

Skin cancer is caused by solar UVR, which is also essential for vitamin D production. DNA damage (thymine dimers: T-T dimers) and vitamin D (25(OH)D) synthesis are both initiated by solar UVB. We aimed to investigate the simultaneous adverse and beneficial effects of solar UVB exposure in holidaymakers. Sun-seekers and skiers (n=71) were observed over 6 days through on-site monitoring, personal diary entries, and recording of personal UVB exposure doses with electronic dosimeters. Urine and blood samples were analyzed for T-T dimers and 25(OH)D, respectively. The volunteers had a statistically significant increase in vitamin D. There were strong associations between UVB exposure and post-holiday levels of T-T dimers and vitamin D, as well as between post-holiday T-T dimers and vitamin D. We conclude that UVB-induced vitamin D synthesis is associated with considerable DNA damage in the skin. These data, on two major health predictors, provide a basis for further field studies that may result in better understanding of the risks and benefits of “real life” solar exposure. However, vitamin D status can be improved more safely through the use of vitamin D dietary supplements

Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: The European prospective mother-child study (NewGeneris)

Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study. Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires. Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.The NewGeneris (Newborns and Genotoxic exposure risks) study was funded by the European Union (EU Contract FOOD-CT-2005-016320). The study was also supported by grants obtained locally, including the Swedish Cancer and Allergy Foundation and the Swedish Research Council Formas, the National Institute for Health Research, UK (programme grant RP-PG-0407-10044), the Norwegian Ministry of Health, the Norwegian Ministry of Education and Research, the Norwegian Research Council/FUGE (grant 151918/S10), the EU funded HiWATE (contract Food-CT-2006-036224), the U.S. National Institutes of Health (NIH)/National Institute of Environmental Health Sciences (contract NO-ES-75558), and the U.S. NIH/National Institute of Neurological Disorders and Stroke (grant 1 UO1 NS 047537-01). M.P. holds a Juan de la Cierva postdoctoral fellowship awarded from the Spanish Ministry of Science and Innovation (JCI-2011-09479

Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris)

Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy. Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires. Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g) Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective