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ER – AhR “receptor cross-talk” and epigenetic memory. Adaptive mechanism vs. the increase in toxicity of environmental pollutants

Praca recenzowana / Peer-reviewed paperWiedza na temat szkodliwości związków chemicznych zawartych we wdychanym powietrzu a także innych ksenobiotyków środowiskowych jest coraz szersza. Skutkuje to wprowadzeniem regulacji prawnych wymuszających ograniczanie emisji zanieczyszczeń do środowiska. Szkodliwość zdrowotną zanieczyszczeń potwierdzają zarówno badania epidemiologiczne, jak i badania laboratoryjne. Bardzo często konsekwencje tego wpływu obserwujemy dopiero po latach. Najlepszym tego przykładem jest wzrost ryzyka chorób dróg oddechowych, będących bezpośrednim efektem narażenia na wysokie stężenia zanieczyszczeń w powietrzu, ale także chorób chronicznych, których ryzyko wydaje się odzwierciedlać wpływ środowiska w okresie płodowym. Do niedawna głównym obszarem badań była ocena wielkości tego ryzyka na podstawie statystycznych analiz zależności przyczynowo-skutkowych. Szybki rozwój biologii molekularnej spowodował, że skoncentrowano się także na zmianach, jakie zanieczyszczenia indukują w szlakach metabolicznych i procesach sygnalizacyjnych w komórce. Pozwoliło to dostrzec nie tylko negatywne skutki zanieczyszczeń, ale także pewne korzystne efekty wynikające z uruchomienia przez organizm procesów adaptacyjnych. Najwięcej uwagi poświęca się interakcji między receptorami aktywowanymi przez zanieczyszczenia środowiska (AhR), a receptorami estrogenowymi (ER) i skutkom, jakie ta „rozmowa receptorów” (ang. cross-talk) wywołuje w ekspresji genów docelowych dla tych receptorów. Zanieczyszczenia środowiska mogą wywoływać zmiany w ekspresji genów zaburzając mechanizm dziedziczenia pozagenowego, zwanego dziedziczeniem epigenetycznym. Zmiany te – jeśli wystąpią w bardzo wczesnym okresie życia płodowego – mogą utrzymywać się w kolejnych pokoleniach, dzięki nośnikom pamięci genetycznej, jaką jest np. metylacja DNA. W zależności od tego, w których genach dochodzi do wyciszenia ekspresji, zjawisko to może wpływać na biologiczne funkcje organizmu, zwiększając przystosowanie do zmieniającego się środowiska, ale może także zwiększać wrażliwość na rozwój chorób chronicznych w życiu dorosłym, ustanawiając pewien wzór ekspresji genów na etapie rozwoju zarodkowego.Knowledge of the harmful effect of air pollution and other environmental xenobiotics is getting broader. This leads to the introduction of mandatory legal regulations limiting the emission of pollutants into the environment. Health harmfulness of pollution is confirmed by both epidemiological and laboratory studies. The consequences of this harmful effect is not only observed almost immediately after the exposure but also after many years. The best example is an increase in the risk of respiratory symptoms which constitute a direct effect of the exposure to high concentration of air pollutants. Chronic conditions occure in adult life can also be caused by the exposure experience during the fetal growth or perinatal period. Until recently, the main area of study was to assess the magnitude of this risk by using statistical analysis. The rapid development of molecular biology allows to focus on the changes that environmental pollution induces in the metabolic pathways and signaling processes in the cell. Therefore, it become possibles to see not only the harmful effects of pollution, but also certain beneficial effects resulting from the induction of adaptive processes in the body. Most attention is paid to the interaction between the receptors activated by environmental pollution (AhR) and estrogen receptors (ER). The effects of this „cross-talk” between receptors influence the expression of their target genes. Environmental exposure can also influence the gene expression profile due to epigenetic mechanism. These changes if they occur very early in fetal life, may persist in subsequent generations through genetic memory kept by the DNA methylation pattern. This phenomenon can affect the biological functions by increasing adaptation to the environment fluctuation or enhancing susceptibility to the development of chronic diseases in adult life.Rozdział został sfinansowany w ramach grantu Ministerstwa Nauki i Szkolnictwa Wyższego Nr N N303 2403 33

Effect of air pollution on menstrual cycle length : a prognostic factor of women's reproductive health

Air pollution can influence women’s reproductive health, specifically menstrual cycle characteristics, oocyte quality, and risk of miscarriage. The aim of the study was to assess whether air pollution can affect the length of the overall menstrual cycle and the length of its phases (follicular and luteal). Municipal ecological monitoring data was used to assess the air pollution exposure during the monitored menstrual cycle of each of 133 woman of reproductive age. Principal component analyses were used to group pollutants (PM10, SO2, CO, and NOx) to represent a source-related mixture. PM10 and SO2 assessed separately negatively affected the length of the luteal phase after standardization (b = −0.02; p = 0.03; b = −0.06; p = 0.02, respectively). Representing a fossil fuel combustion emission, they were also associated with luteal phase shortening (b = −0.32; p = 0.02). These pollutants did not affect the follicular phase length and overall cycle length, neither in single- nor in multi-pollutant models. CO and NOx assessed either separately or together as a traffic emission were not associated with overall cycle length or the length of cycle phases. Luteal phase shortening, a possible manifestation of luteal phase deficiency, can result from fossil fuel combustion. This suggests that air pollution may contribute to fertility problems in women

Paternal investment and low birth weight : the mediating role of parity

According to life-history theory, paternal investment affects the well-being of offspring. We hypothesized that environmental stress caused by a lack of paternal investment may diminish maternal resource allocation during pregnancy, especially for women who already have dependent children. Our study was conducted on a representative group of more than 80,500 singleton, live-born, full-term infants born in Krakow, Poland in the period 1995-2009. Birth data were obtained from the birth registry. We found that missing data about fathers (a proxy measure of low paternal investment) was associated with higher probability of multiparous mothers giving birth to low-birth-weight infants (1.48; 95% CI 1.05-2.08), but this was not the case with primiparous mothers (1.19; 95% CI 0.89-1.59). The statistically significant synergistic effect between parity and paternal investment was found (Synergy Factor = 2.12; 95% CI 1.47-3.05, p<0.001). These findings suggest that in situations of low paternal investment, multiparous mothers face trade-offs between investing in existing versus unborn children, therefore investment in the latter is lower. Such a strategy may benefit maternal fitness due to investment in older children, who have higher reproductive value

Polifenole roślinne i ich rola w medycynie

Ze wstępu: "Dane epidemiologiczne wskazują na bezpośrednią zależność między wielkością spożycia warzyw i owoców a redukcją ryzyka chorób degeneracyjnych, w szczególności nowotworów [1]. Sposób żywienia współczesnego człowieka najczęściej nie dostarcza zalecanych składników odżywczych w proporcjach optymalnych. Nie dostarcza także wystarczającej ilości tzw. składników nieodżywczych, do których należą zawarte w pokarmie zarówno witaminy i związki mineralne, jak i roślinne polifenole. To właśnie te ostatnie wraz z witaminami antyutleniąjącymi odgrywają największą rolę w prozdrowotnym działaniu warzyw i owoców. Odpowiednia ich ilość dostarczona do organizmu sprzyja stabilizacji genetycznej, a w szczególności zmniejsza poziom endogennych uszkodzeń oksydacyjnych DNA. Co prawda w ostatnich latach rośnie świadomość konsekwencji, do jakich może prowadzić niewłaściwe odżywianie, ale niestety „przyspieszony” tryb życia, a także moda na suplementy żywieniowe wynikająca z przekonania o ich zbawiennym działaniu, sprzyjają szybkiemu wzrostowi spożycia najrozmaitszych suplementów żywnościowych, a zwłaszcza tych zawierających ekstrakty roślinne. Często zawarte w nich polifenole, co udokumentowane jest w literaturze światowej, są zażywane w stężeniach wielokrotnie przekraczających stężenia w zjadanych warzywach i owocach, nawet w diecie wegetarian [2]. Może to stanowić także zagrożenie zdrowia."(...

The level of endogenous DNA damage in lymphocytes isolated from blood is associated with the fluctuation of 17\beta-estradiol concentration in the follicular phase of healthy young women

The aim of this study was to evaluate whether the differences in plasma 17β-estradiol concentration in early and late follicular phases of the menstrual cycle can affect the level of endogenous DNA damage in lymphocytes assessed by comet assay, and whether the extent of this damage in the follicular phase is associated with the genotype of catechol-O-methyltransferase (COMT). The level of DNA damage was positively correlated with 17β-estradiol concentration only in the late follicular phase. Subjects with the COMT L/L homozygous mutated variant revealed more DNA damage as compared to individuals with the COMT wild-type and heterozygous (H/L+HH) genotype

Detection of X-Ray Damage Repair by the Immediate Versus Delayed Plating Technique is Dependent on Cell Shape and Cell Concentration

A method commonly used to measure the ability of cells to repair potentially lethal damage (PLD) is to compare immediate plating (IP) and delayed plating (DP) survival. Lower cell survival under IP conditions relative to that after DP conditions has been interpreted to indicate a higher ability of cells to repair potentially lethal damage (PLO) under DP conditions. However, this IP radiosensitization has not been observed in several cell lines and tumor models. IP conditions involve treatment of cells with trypsin and plating them into fresh growth medium. We have investigated the possibility that radiosensitization under IP conditions may be related to both the cell-shape and the nutrient concentration in growth medium (GM, MEM+15% serum). This idea predicts that the IP and DP survival of spheroids will show a response similar to the IP survival of cells in monolayers and that the IP and DP survival of crowded monolayer cells in high densities will be the same. Chinese hamster V79 cells grown in monolayers (spread cells) and spheroids (clumps of round cells) were used. The IP survival was lower than the DP survival for spread log phase monolayer cells but not for round log phase cells in spheroids. Radiosensitization of cells by fresh (as opposed to spent) growth medium was absent for high density plateau phase cells in monolayers at or above 2x106 cells/ml. However, PLO repair could be demonstrated in spheroid cells and in high density plateau phase cultures by exposing cells to hyperthermia or hypertonic saline. Comparison of immediate plating versus delayed plating survival detects PLO repair only in well spread low density monolayer cells, but not in round spheroid cells nor in dense monolayer cells at \u3e 107 cells/25 cm2 flask/5 ml medium. The absence of a difference between IP and DP cell survival does not mean that PLO repair is absent. Incorrect prediction of tumor response to radiotherapy can occur when PLO repair capacity is assayed as a ratio of DP/IP survival. More than one method must be used to measure the capacity of cells to repair their PLO

High tea consumption diminishes salivary 17beta-estradiol concetration in Polish women

Artykuł recenzowany / peer-reviewed articleWe hypothesized that among reproductive-age women consuming large quantities of tea, the production of estradiol would be suppressed. It has been shown that catechins and theaflavines, the major constituents of tea, inhibit aromatase, an enzyme which catalyses the conversion of androgens to estrogens. Our study included Polish women living in urban (N=61) and rural (N=48) areas. Women collected daily saliva samples for one complete menstrual cycle and filled out dietary questionnaires. Saliva samples were analyzed by radioimmunoassay for concentration of 17-β estradiol (E2). Women with high (above the median) average daily consumption of black tea had reduced levels of salivary E2, in comparison with women who drank less black tea (below median). This effect was observed within the whole study group, as well as separately within urban (p = 0.0006) and rural (p = 0.013) groups. High intake of the sum of subclasses of tea catechins and epigallocatechin gallate, assessed using the USDA database [http://www.nal.usda.gov], was also associated with lower concentrations of E2 within all women (p = 0.01 and p = 0.0001, respectively) and within the urban group (p = 0.0001 and p = 0.004, respectively). Similar relationships were observed between the sum of subclasses of theaflavines and thearubigines and E2 levels for the whole group (p = 0.002) and for urban women (p = 0.02). Women with high consumption of tea had lower levels of E2 concentration throughout the entire menstrual cycle. These results may have implications for reducing hormone-related cancer risk by a relatively easy dietary intervention.the State Committee for Scientific Research, Warsaw, Poland, project No. 3 P05E 016 25 and 6 P05D 112 20, the Radcliffe Institute of Advanced Study, Harvard University and the Norwegian Cancer Society

Ocena stanu odżywienia organizmu: practicum

Praca recenzowana / peer-reviewed pape