Trichoplax adhaerens, the only known species of Placozoa is likely to be closely related to an early metazoan that preceded branching of Cnidaria and Bilateria. This animal species is surprisingly well adapted to free life in the World Ocean inhabiting tidal costal zones of oceans and seas with warm to moderate temperatures and shallow waters. The genome of T. adhaerens (sp. Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues. In the case of RXR, the sequence identity to human RXR alpha reaches 81% in the DNA binding domain and 70% in the ligand binding domain. We show that T. adhaerens RXR (TaRXR) binds 9-cis retinoic acid (9-cis-RA) with high affinity, as well as high specificity and that exposure of T. adhaerens to 9-cis-RA regulates the expression of the putative T. adhaerens orthologue of vertebrate L-malate-NADP+ oxidoreductase (EC 1.1.1.40) which in vertebrates is regulated by a heterodimer of RXR and thyroid hormone receptor. Treatment by 9-cis-RA alters the relative expression profile of T. adhaerens nuclear receptors, suggesting the existence of natural ligands. Keeping with this, algal food composition has a profound effect on T. adhaerens growth and appearance. We show that nanomolar concentrations of 9-cis-RA interfere with T. adhaerens growth response to specific algal food and causes growth arrest. Our results uncover an endocrine-like network of nuclear receptors sensitive to 9-cis-RA in T. adhaerens and support the existence of a ligand-sensitive network of nuclear receptors at the base of metazoan evolution.

• Klíčová slova
• 9-cis retinoic acid, COUP, ERR, Food, HNF4, Nuclear receptor, RXR, Trichoplax adhaerens,
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Radon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking. METHODS: We conducted a case-cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977-1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate. RESULTS: Under a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI -0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI -0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI -0.04 to 10.32) in the period 5-14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure. CONCLUSIONS: We observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion.

• Klíčová slova
• cancer, ionizing, miners, radiation, radon,
• MeSH
• dceřiné produkty radonu škodlivé účinky   MeSH
• dospělí MeSH
• horníci statistika a číselné údaje   MeSH
• incidence MeSH
• kohortové studie MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic epidemiologie   MeSH
• nádory vyvolané zářením epidemiologie   MeSH
• nádory epidemiologie   MeSH
• pracovní expozice škodlivé účinky   MeSH
• radon škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• uran MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• dceřiné produkty radonu MeSH
• radon MeSH
• uran MeSH

The present study is based on 9978 Czech uranium miners with 1141 lung cancer deaths observed in an updated follow-up 1952-2010 and corresponding to 31 years of mean follow-up. The objectives of the study are to obtain more reliable estimates for the exposure-response relationship, including factors that modify this relationship. Lung cancer in relation to cumulative exposure to radon decay products is linear with substantial modifications by time since exposure, age at exposure and exposure rate using exposure windows. The crude excess relative risk (ERR) per unit exposure in working level months (WLM) in the cohort is 0.0097 (90% confidence interval (CI) 0.0074-0.0127). The ERR/WLM corresponding to exposure rates below 7 working levels (WL) is substantially higher - 0.0145 (90% CI 0.0109-0.0193). In the final model, the inverse effect of exposure rate is observed for high exposure rates >7 WL with the ERR/WLM reduced to 31%. The ERR/WLM decreases to 32% and 9% in periods 20-29 and 30 +years since exposure in comparison to the period of 5-19 years since exposure. Simultaneously, the ERR/WLM decreases with age at exposure - 63% and 49% at ages 30-39 and 40 +years in comparison to age at exposure <30 years.

• MeSH
• dávka záření MeSH
• dospělí MeSH
• hornictví * MeSH
• interval spolehlivosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic mortalita   MeSH
• nádory vyvolané zářením mortalita   MeSH
• následné studie MeSH
• nemoci z povolání mortalita   MeSH
• Poissonovo rozdělení MeSH
• pracovní expozice škodlivé účinky   MeSH
• radon chemie   MeSH
• riziko MeSH
• rozdělení chí kvadrát MeSH
• senioři MeSH
• uran chemie   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• radon MeSH
• uran MeSH

The electrographic respiratory response (ERR) was elicited by nasal air flow in the brain of the frog and turtle. It had the shape of a spindle of high voltage rhythmic activity and was propagated from the olfactory bulb predominantly into the ipsilateral hippocampal region in the frog and into the pyriform cortex in the turtle. In both animals, thalamic propagation of the ERR was also found. In both animals epileptic electrographic phenomena, were enhanced, created by local penicillin application. In the turtle epileptic electrographic manifestations were also elicited in the intact brain by simple nasal air insufflation. Diazepam (intraperitoneal administration) had no effect either on the ERR or on its triggering effect on epileptic phenomena. The possible physiological and pathophysiological interpretations of these findings are discussed.

• MeSH
• dýchání * MeSH
• elektroencefalografie * MeSH
• epilepsie patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• králíci MeSH
• krysa rodu Rattus MeSH
• mozková kůra patofyziologie   MeSH
• nos fyziologie   MeSH
• želvy fyziologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The endocrine disruptor Bisphenol A (BPA), a widely employed molecule in plastics, has been shown to affect several biological processes in vertebrates, mostly via binding to nuclear receptors. Neurodevelopmental effects of BPA have been documented in vertebrates and linked to neurodevelopmental disorders, probably because some nuclear receptors are present in the vertebrate brain. Similarly, endocrine disruptors have been shown to affect neurodevelopment in marine invertebrates such as ascidians, mollusks or echinoderms, but whether invertebrate nuclear receptors are involved in the mode-of-action is largely unknown. In this study, we assessed the effect of BPA on larval brain development of the ascidian Phallusia mammillata. We found that BPA is toxic to P. mammillata embryos in a dose-dependent manner (EC50: 11.8μM; LC50: 21μM). Furthermore, micromolar doses of BPA impaired differentiation of the ascidian pigmented cells, by inhibiting otolith movement within the sensory vesicle. We further show that this phenotype is specific to other two bisphenols (BPE and BPF) over a bisphenyl (2,2 DPP). Because in vertebrates the estrogen-related receptor gamma (ERRγ) can bind bisphenols with high affinity but not bisphenyls, we tested whether the ascidian ERR participates in the neurodevelopmental phenotype induced by BPA. Interestingly, P. mammillata ERR is expressed in the larval brain, adjacent to the differentiating otolith. Furthermore, antagonists of vertebrate ERRs also inhibited the otolith movement but not pigmentation. Together our observations suggest that BPA may affect ascidian otolith differentiation by altering Pm-ERR activity whereas otolith pigmentation defects might be due to the known inhibitory effect of bisphenols on tyrosinase enzymatic activity.

• Klíčová slova
• Ascidian, Bisphenol A, Estrogen-related receptor, Invertebrate, Neurodevelopment, Otolith,
• MeSH
• benzhydrylové sloučeniny chemie   toxicita   MeSH
• buněčná diferenciace účinky léků   MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• embryo nesavčí účinky léků   MeSH
• estrogenní receptor ERRalfa MeSH
• fenoly chemie   toxicita   MeSH
• larva účinky léků   metabolismus   MeSH
• mozek cytologie   embryologie   MeSH
• organogeneze * účinky léků   MeSH
• otolitová membrána cytologie   účinky léků   MeSH
• pigmentace * účinky léků   MeSH
• pohyb buněk účinky léků   MeSH
• receptory pro estrogeny antagonisté a inhibitory   metabolismus   MeSH
• testy toxicity MeSH
• Urochordata cytologie   embryologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• chemické látky znečišťující vodu MeSH
• fenoly MeSH
• receptory pro estrogeny MeSH

OBJECTIVES: Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners. METHODS: The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure. RESULTS: In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. CONCLUSIONS: This new large, pooled study confirms and supports a linear exposure-response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.

• Klíčová slova
• Cancer, Miners, Radiation, Radon,
• MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic * etiologie   MeSH
• nádory vyvolané zářením * epidemiologie   etiologie   MeSH
• nemoci z povolání * epidemiologie   etiologie   MeSH
• pracovní expozice * škodlivé účinky   MeSH
• proteiny regulující apoptózu MeSH
• radon * škodlivé účinky   MeSH
• uran * škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• proteiny regulující apoptózu MeSH
• radon * MeSH
• uran * MeSH

Eleven underground miners studies evaluated the risk of lung cancer from exposure in underground mines. Nearly 68,000 miners were included in the joint study, contributing to nearly 2700 lung cancers. The resulting model of the Biological Effects of Ionizing Radiation (BEIR) VI Committee considered linear exposure response relationship, which was modified by time since exposure (TE), attained age and exposure rate. The effect of age at exposure (AE) was not explicitly evaluated. The presentation aims to show that the modifying effect of AE is substantial if time-since-exposure modification is simultaneously used in the model. When the excess relative risk per unit exposure (ERR/WLM) is adjusted for TE, the ERR/WLM corresponding to AE<15 is 0.013 and in subsequent categories decreased gradually up to the AE of 40 and more years, which was only 0.004. In comparison with the BEIR VI model, the present model predicts higher risks at younger ages and the risk decreases more rapidly.

• MeSH
• dospělí MeSH
• hornictví * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory plic etiologie   MeSH
• nádory vyvolané zářením etiologie   MeSH
• následné studie MeSH
• pracovní expozice škodlivé účinky   MeSH
• prognóza MeSH
• radioaktivní znečišťující látky škodlivé účinky   MeSH
• radon škodlivé účinky   MeSH
• rizikové faktory MeSH
• senioři MeSH
• uran škodlivé účinky   MeSH
• věkové faktory MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• radioaktivní znečišťující látky MeSH
• radon MeSH
• uran MeSH

BACKGROUND: This study aims to estimate the association between radon and site-specific cancer mortality among a large contemporary cohort of male uranium miners. METHODS: Annual occupational radon exposure was estimated based on a worker's duration of underground mining in a year and estimates of potential alpha energy of radon progeny in their location of work. Cancer mortality over the period 1977-1992 was ascertained for a cohort of 16 434 male underground uranium miners employed in the Czech Republic between 1946 and 1992. Poisson regression was used to estimate relationships between cumulative radiation exposure (in working level months [WLM]) and site-specific cancer mortality. RESULTS: Radon is positively associated with lung cancer mortality (excess relative rate [ERR] per 100 WLM = 0.2; 95% confidence interval [CI]: 0.10, 0.37). The best fit of the dose-response relationship between radon and lung cancer mortality was linear and estimates of radon-lung cancer associations varied by windows of time-since-exposure. Positive associations between radon and several types of cancer other than lung cancer were identified, notably chronic lymphocytic leukemia (CLL) (ERR/100 WLM = 0.24; 95% CI: [not determined [ND], 5.10]) and extrathoracic cancer (ERR/100 WLM = 0.12; 95% CI: [ND, 0.69]). We observed no associations between radon and stomach cancer, nor between radon and several hematopoietic cancer subtypes. CONCLUSIONS: This study confirms the established radon-lung cancer association and suggests that radon may also be associated with other types of cancer mortality. Further investigations of extrathoracic and CLL cancer, with the aim of obtaining more precise estimates, are warranted to understand associations between radon and cancers other than lung.

• Klíčová slova
• cancer, lung cancer, radon, uranium mining,
• MeSH
• chronická lymfatická leukemie etiologie   mortalita   MeSH
• hornictví * MeSH
• lidé MeSH
• nádory plic etiologie   mortalita   MeSH
• nádory vyvolané zářením mortalita   MeSH
• nemoci z povolání etiologie   mortalita   MeSH
• Poissonovo rozdělení MeSH
• pracovní expozice škodlivé účinky   MeSH
• radon toxicita   MeSH
• uran * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• radon MeSH
• uran * MeSH

BACKGROUND: Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated. OBJECTIVES: To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings. METHODS: We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer. RESULTS: The analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM=1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages <55 y, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ≥35 years of age and at annual exposure rates of <0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates. DISCUSSION: Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669.

• MeSH
• dceřiné produkty radonu MeSH
• horníci * MeSH
• lidé MeSH
• nádory plic * MeSH
• nádory vyvolané zářením * epidemiologie   etiologie   MeSH
• nemoci z povolání * epidemiologie   etiologie   MeSH
• pracovní expozice * MeSH
• radon * MeSH
• uran * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• dceřiné produkty radonu MeSH
• radon * MeSH
• uran * MeSH

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

• Klíčová slova
• Cohort study, Lifetime risk, Lung cancer, Mortality, Radon, Uranium miners,
• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory plic * epidemiologie   etiologie   MeSH
• nádory vyvolané zářením * epidemiologie   etiologie   MeSH
• nemoci z povolání * epidemiologie   MeSH
• pracovní expozice * škodlivé účinky   MeSH
• proteiny regulující apoptózu MeSH
• radon * škodlivé účinky   MeSH
• uran * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny regulující apoptózu MeSH
• radon * MeSH
• uran * MeSH