Analysis of the cancer occurrence related to natural radioactivity in the Rio Grande do Norte State, Brazil.

The state of Rio Grande do Norte, located in the Northeast region of Brazil, has areas of granites and pegmatites with minerals that have varying concentrations of uranium. Consequently, high concentrations of radon gas, a carcinogenic substance for humans, can occur. The present study aimed to assess the occurrence of cancer and its association with exposure to sources of natural radioactivity using geological and geophysical information in the aforementioned state. The spatial dependence of pulmonary, breast, stomach, leukemia, and skin cancer cases with the location of radioisotope sources were analyzed using geoprocessing tools. The geoprocessing analysis showed a differential pattern of uranium emission throughout the state, with the highest emission from areas with pegmatites outcrops. A spatial dependency of cancer cases was shown (Moran index: 0.43; p < 0.01). Moreover, a higher rate of natural radioactivity-cancer cases was associated with the high-intensity natural radioactivity areas: odds ratio:1.21 (95% CI 1.20; 1.23), following the same pattern when separately compared the different related types of cancer. These results highlight the importance of natural radioactivity as a public health problem in the Brazilian environmental scenario, confirming the need for further studies as the first toward understanding and implementing health management strategies mitigating the exposures, especially in areas of environmental risk.

Oxidative genomic damage in humans exposed to high indoor radon levels in Northeast Brazil.

Radon gas inhalation is the main source of exposure to ionizing radiation by humans. There is still lack in knowledge concerning the chronic and indirect effects of exposure to this carcinogenic factor. Therefore, the aim of this work is to analyze the levels of oxidative genomic damage in inhabitants of a medium-high background radiation area (HBRA) (N = 82) in Northeastern Brazil and compare them with people living in a low background radiation area (LBRA) (N = 46). 8-hydroxy-2-deoxyguanosine (8-OHdG) was quantified in urine, Ser326Cys polymorphism was determined in the hOGG1 gene and indoor radon was measured. HBRA houses had 6.5 times higher indoor radon levels than those from LBRA (p-value < 0.001). The 8-OHdG mean (95% confidence interval) were significantly different, 8.42 (5.98-11.9) ng/mg creatinine and 29.91 (23.37-38.30) ng/mg creatinine for LBRA and HBRA, respectively. The variables representing lifestyle and environmental and occupational exposures did not have a significant association with oxidized guanosine concentrations. On the other hand, lower 8-OHdG values were observed in subjects that had one mutant allele (326Cys) in the hOGG1 gene than those who had both wild alleles (Ser/Ser (p-value < 0.05). It can be concluded that high radon levels have significantly influenced the genome oxidative metabolism and hOGG1 gene polymorphism would mediate the observed biological response.

Ensaios de toxicidade para avaliagao de águas superficiais estuarinas usando Nitocra sp. como organismo-teste alternativo / Toxicity tests for the evaluation of estuarine surface waters using Nitocra sp. as an alternative test organism

Resumo A crescente poluigao de ambientes marinhos e estuarinos por descarga de efluentes é um problema mundial. Os ensaios ecotoxicológicos vem sendo amplamente utilizados para monitorar os efeitos deste tipo de poluigao e, atualmente sao incorporados na legislagao ambiental de diversos países, nomeadamente no Brasil. Contudo, sao poucos os estudos realizados em áreas costeiras e a padronizagao de métodos com organismos nativos, representativos de ecossistemas locais, é insuficiente. Nitocra sp. tem sido eficientemente utilizado em ensaios ecotoxicológicos com sedimentos e águas intersticiais, sendo neces-sário avaliar a sua adequagao na análise de águas superficiais estuarinas. Amostras pontuais de agua do baixo estuário Jundiaí -Potengi (EJP) foram coletadas mensalmente durante 18 meses, em áreas com (CE) e sem (SE) recegao de efluentes tratados. Nitocra sp. e Mysidopsis juniae (espécie padronizada) foram os organismos teste utilizados nos ensaios ecotoxicológicos. Efeitos letais (taxa de mortalidade) e subletais (taxa de reprodugao) foram analisados considerando a caracterizagao microbiológica e físico-química das amostras testadas. Os teores de oxigenio dissolvido, salinidade, demanda bioquímica de oxigenio, nitrogenio amoniacal e amoniacal total, nitrogenio total, óleos e graxas, sólidos suspensos e sedimentáveis, potássio total e coliformes termotolerantes determinados nas amostras CE e SE, traduzem diferentes níveis de poluigao nos locais amostrados. As cartas-controle de Nitocra sp. e M. juniae indicaram boa reprodutibilidade laboratorial, e apesar dos organismos teste terem exibido diferentes perfis ecotoxicológicos, o aumento da taxa de mortalidade de ambos esteve associada a emissao de esgoto tratado. O uso de diferentes organismos teste favorece a representatividade dos ensaios ecotoxicológicos. Considerando o perfil de Nitocra sp. no monitoramento do EJP, o seu estabelecimento como organismo-teste padronizado necessita de mais estudos, incluindo a utilizagao de nauplii em bioensaios.

Abstract Increasing pollution of marine and estuarine environments from wastewater discharge is a worldwide problem. Eco-toxicological tests are widely used to monitor the effects of this type of pollution and are currently being incorporated into the environmental legislation of several countries, including Brazil. However, few studies have been conducted in coastal areas, and standardization of methods with native organisms representative of local ecosystems is insufficient. Nitocra sp. has been efficiently used in ecotoxicological tests with sediments and interstitial waters, and its suitability for estuarine surface water analysis needs to be assessed. Point samples from the lower Jundiaí-Potengi estuary (JPE) in areas with (CE) and without (SE) discharge of treated effluents were collected monthly for 18 months. Nitocra sp. and Mysidopsis juniae (standardized species) were the test organisms used in the ecotoxicological assays. The lethal (mortality rate) and sublethal (reproduction rate) effects were analyzed considering the microbiological and physicochemical characterization of the tested samples. Dissolved oxygen, salinity, biochemical oxygen demand, ammoniacal and total ammoniacal nitrogen, total nitrogen, oils and greases, suspended and settleable solids, total potas-sium and thermotolerant coliform bacteria determined in samples from CE and SE, reflect varying levels of pollution at the sampled sites. The control charts of Nitoera sp. and M. juniae indicated good reproducibility in the laboratory, and although the test organisms had different ecotoxicological profiles, the mortality rate of both organisms was related to the discharge of treated wastewater. The use of different test organisms increases the representativeness of the ecotoxicological tests. Given the profile of Nitoera sp. in JPE monitoring, further studies, including the use of nauplii in bioassays, are needed to establish it as standardized test organism.

Validagao da espécie Dendrocephalus brasiliensis como organismo teste de água doce em estudos ecotoxicológicos para avaliagao de fármacos utilizados no tratamento da COVID-19 / Validation of the species Dendrocephalus brasiliensis as a freshwater test organism in ecotoxicological studies for evaluation of pharmaceuticals used in the treatment of COVID-19

Resumo Os contaminantes emergentes (CE), sao substáncias químicas (fármacos, produtos de higiene pessoal, drogas ilícitas entre outros) que estao presentes no ambiente como consequéncia da atividade antrópica e a falta de adequagao dos processos convencionais de tratamento de água e esgoto que nao logram remové-los eficientemente. Na atualidade o uso disseminado e desmedido de fármacos no tratamento da pandemia de COVID 19 tem aumentado a preocupagao dos impactos decorrentes da contaminagao por fármacos em ambientes aquáticos, consequéncia da liberagao no ambiente de grandes quantidades destes compostos. Assim, estudos de ecotoxicidade aquática sao fundamentais para avaliar o efeito de substáncias químicas tóxicas nas análises de impactos ambientais, sobretudo quando utilizado organismos representativos da biota aquática local, garantindo assim, maior confiabilidade e representatividade dos resultados obtidos. Diante disto, o objetivo deste trabalho foi validar a utili-dade do Dendrocephalus brasiliensis (Branchoneta) espécie autóctone do nordeste brasileiro como organismo teste para estudos de ecotoxicidade de fármacos utilizados no tratamento da COVID 19. Testes ecotoxicológicos utilizando D. brasiliensis foram realizados utilizando solugóes dos fármacos paracetamol, hidroxicloroquina, ivermectina e ibuprofeno, em concentragóes de 0,0025 até 600,0 mg/L seguindo os protocolos descritos pela Associagao Brasileira para Normas Técnicas (ABNT) para toxicidade aguda, protocolo padronizado para a realizagao do ensaio ecotoxicológicos utilizando como organismo teste a Daphnia magna, o qual foi empregada como referencia para comparar o padrao de resposta. Com os resultados obtidos foi realizado o cálculo da CL50-48h considerando como desfecho a morte dos organismos, ivermectina (< 0,0025 - < 0,0025), hidroxicloroquina (3,70 - 14,09), ibuprofeno (12,25 - 107,52), paracetamol (8,53 - 9,61), resultados CL50-48h mg/l D. magna e D. brasiliensis respectivamente. Os resultados obtidos mostraram um padrao diferenciado dependente da espécie e do fármaco analisado observando-se uma menor sensibilidade frente a exposigao da D. brasiliensis em comparagao a D. magna demonstrando a valia da D. brasiliensis como organismo teste. Pesquisas futuras dirigidas a analisar as potenciais interagóes destes fármacos em concentragóes ambientais reais sao necessárias para completar a validagao e ter uma aproximagao dos eventos acometidos em ambientes impactados por estes fármacos.

Abstract Emerging contaminants (EC) are chemical substances (pharmaceuticals, personal hygiene products, illicit drugs, among others) that are present in the environment because of human activity and the lack of adequacy of conventional water and sewage treatment processes that do not manage to remove them efficiently. Currently, the widespread and excessive use of drugs in the treatment of the COVID 19 pandemic has increased concern about the impacts resulting from contamination by drugs in aquatic environments, because of the release into the environment of large amounts of these compounds. Thus, aquatic ecotoxicity studies are essential to evaluate the effect of toxic chemical substances in the analysis of environmental impacts, especially when using representative organisms of the local aquatic biota, thus ensuring greater reliability and representativeness of the results obtained. In view of this, the objective of this work was to validate the usefulness of Dendrocephalus brasiliensis (Branchoneta), an autoch-thonous species from northeastern Brazil as a test organism for ecotoxicity studies of drugs used in the treatment of COVID 19. Ecotoxicological tests using D. brasiliensis were performed using drug solutions paracetamol, hydroxychloroquine, ivermectin and ibuprofen, in concentrations from 0.0025 to 600.0 mg/L following the protocols described by the Brazilian Association for Technical Norms (ABNT) for acute toxicity, standardized protocol for carrying out the ecotoxicological assay using as a test organism Daphnia magna, which was used as a reference to compare the response pattern. Based on the results obtained, the LC50-48h was calculated considering the death of organisms, ivermectin (< 0.0025 - < 0.0025), hydroxychloroquine (3.70 - 14.09), ibuprofen (12.25 - 107.52), paracetamol (8.53 - 9.61), results LC50-48h mg/l D. magna and D. brasiliensis respectively. The results obtained showed a differenti-ated pattern depending on the species and the analyzed drug, observing a lower sensitivity to exposure of D. brasiliensis compared to D. magna, demonstrating the value of D. brasiliensis as a test organism. Future research aimed at analyzing the potential interac-tions of these drugs at real environmental concentrations is necessary to complete the validation and to have an approximation of the events affected in environments impacted by these drugs.

A vigilancia farmacológica no cenário brasileiro do sáculo 21 / Pharmacological surveillance in the Brazilian scenario of the 21st century / La vigilancia farmacológica en el escenario brasileño del siglo XXI

Resumo Os estudos em vigilancia farmacológica e ecofarmacológicas possibilitam o monitoramento, identificagao e minimi-zagao de efeitos nocivos advindos do uso de medicamentos. Diante disso, o presente estudo teve como objetivo descrever o cenário atual da farmacoepidemiologia e ecofarmacovigilancia no Brasil, no que se refere a produgao, registro, comerciali-zagao e uso de medicamentos. Foi realizado um levantamento sistemático, através dos bancos de dados PubMed/Medline, Lilacs e SciELO, cuja temática envolveu pesquisas em farmacoeconomia, farmacovigilancia, ecofarmacovigilancia e estudo da utilizagao de medicamentos no Brasil de 2001 a 2019. As publicagóes distribuíram-se de forma desigual entre as regióes brasileiras. Pacientes hipertensos, oncológicos e as gestantes foram os grupos de risco mais citados e os antimicrobianos, psicotrópicos e antineoplásicos os grupos farmacológicos mais discutidos. Custo de cuidados em saúde foi a temática mais abordada no contexto da farmacoeconomia e grande parte dos trabalhos destinou-se a análise e obtengao de dados referentes ao uso de medicamentos e suas reagóes adversas. Em relagao a ecofarmacovigilancia nao foram encontradas publicagóes no Brasil que contemplem essa área. Apesar dos avangos da legislagao farmacoepidemiológica e melhorias nos processos de fiscalizagao, no que tange a vigilancia da produgao, registro, comercializagao e uso de medicamentos, ainda permanecem carencias, quanto ao aporte de uma visao científica direcionada, sobretudo ao gerenciamento e diferentes usos dos recursos terapéuticos, e económicos do sistema de saúde brasileiro, bem como uma visao ambiental referente ao uso de medicamentos.

Abstract Studies in pharmacological and ecopharmacological surveillance make it possible to monitor, identify and minimize harmful effects arising from the use of drugs. Therefore, the present study aimed to describe the current scenario of pharmacoepidemiology and ecopharmacovigilance in Brazil, about the production, registration, marketing, and use of medicines. A systematic survey was carried out through the PubMed/Medline, Lilacs, and SciELO databases, whose theme involved research in pharmacoeconomics, pharmacovigilance, ecopharmacovigilance, and the study of drug use in Brazil from 2001 to 2019. Publications were unevenly distributed between Brazilian regions. Hypertensive patients, cancer patients, and pregnant women were the most cited risk groups, and antimicrobials, psychotropics, and antineoplastics were the most discussed pharmacological groups. Cost of health care was the most discussed topic in the context of pharmacoeconomics and most of the work was aimed at analyzing and obtaining data regarding the use of drugs and their adverse reactions. Regarding ecopharmacovigilance, no publications were found in Brazil covering this area. Despite advances in pharmacoepidemiological legislation and improvements in inspection processes, regarding the surveillance of the production, registration, commercialization, and use of medicines, there are still gaps regarding the contribution of a directed scientific vision, especially to the management and different uses of resources. therapeutic and economic aspects of the Brazilian health system, as well as an environmental vision regarding the use of medicines.

Resumen Los estudios de vigilancia farmacológica y ecofarmacológica permiten controlar, identificar y minimizar los efectos nocivos derivados del uso de los medicamentos. Ante esto, el presente estudio tuvo como objetivo describir el escenario actual de la farmacoepidemiología y la ecofarmacovigilancia en Brasil, en relación con la producción, el registro, la comercialización y el uso de los medicamentos. Se realizó una encuesta sistemática, a través de las bases de datos PubMed/Medline, Lilacs y SciELO, cuya temática involucró investigaciones sobre farmacoepidemiología, farmacovigilancia, ecofarmacovigilancia y estudio del uso de medicamentos en Brasil desde 2001 hasta 2019. Las publicaciones se distribuyeron de forma desigual entre las regiones brasileñas. Los pacientes hipertensos, los pacientes oncológicos y las mujeres embarazadas fueron los grupos de riesgo más citados y los antimicrobianos, los psicotrópicos y los antineoplásicos fueron los grupos farmacológicos más discutidos. El coste de la asistencia sanitaria fue el tema más abordado en el contexto de la farmacoeconomía y la mayoría de los trabajos estaban dirigidos a analizar y obtener datos sobre el uso de los medicamentos y sus reacciones adversas. En cuanto a la ecofarmacovigilancia, no se encontraron publicaciones en Brasil que aborden esta área. A pesar de los avances en la legislación farmacoepidemiológica y de las mejoras en los procesos de inspección, en lo que respecta a la vigilancia de la producción, registro, comercialización y uso de los medicamentos, todavía falta una visión científica dirigida, sobre todo, a la gestión y a los diferentes usos de los recursos terapéuticos y económicos del sistema de salud brasileño, así como una visión ambiental en cuanto al uso de los medicamentos.

Bioaccumulation of total mercury, copper, cadmium, silver, and selenium in green turtles (Chelonia mydas) stranded along the Potiguar Basin, northeastern Brazil.

Sea turtles face several threats and pollution has become a major concern for their conservation worldwide. We analyzed samples of the liver, muscles, and kidneys of 38 Chelonia mydas stranded along the Potiguar Basin, northeastern Brazil, between 2015 and 2018 to determine the total Hg concentration (THg), as well as the concentrations of Cu, Cd, Ag, and Se. The relation between turtle size and element concentrations revealed a negative correlation for THg and Se (liver, muscles, and kidneys), Cu and Cd (liver and kidneys) and a positive correlation for Ag in the three organs analyzed. Concentrations of THg, Cu, Ag, and Se were high in the liver, highlighting the Cu concentration (median = 25.1150 µg g-1 w.w.), while the kidneys had the highest Cd levels (median = 12.2200 µg g-1 w.w.). There was significant difference between element concentrations and the three organs analyzed, except for Ag and Se concentrations in the muscle and kidney samples. Our study showed that green turtles found in Potiguar Basin, northeastern Brasil, have bioaccumulated inorganic elements which indicate the need of further investigations on the environmental quality of the region.

Diosgenin induces genotoxic and mutagenic effects on HepG2 cells.

Yam roots and other plants from Dioscorea genus have cultural, nutritional and economic importance to tropical and subtropical regions and have a great amount of diosgenin in its composition. In the present study the cytotoxic, genotoxic and mutagenic potential of diosgenin on HepG2 cells was investigated. Cytotoxicity was assessed using MTT and clonogenic assay. Genotoxic and mutagenic effects were performed using single cell gel electrophoresis and cytokinesis-block micronucleus assay, respectively. A reduction on cell viability was observed due to diosgenin treatment at concentrations higher than 30 µM. A genotoxic effect was shown by comet assay and CBMN. Besides, an increase in micronucleus frequency along with a significant cytostatic effect were observed. Diosgenin elicited DNA damage on HepG2 cells which could not be efficiently repaired contributing to the mutagenic effect observed. Those results suggest that diosgenin deleterious effect could take place through genetic instability, fact that affects the normal cell cycle, leading to cell's death.

Influence of natural radon and metal contamination on surface water quality from a Brazilian Semiarid Region / Influência da contaminação natural pelo radônio e metais na qualidade das águas superficiais da Região Semiárida Brasileira

The Brazilian semiarid region presents some adverse environmental conditions for the settled population such as a restricted water availability and the presence of radon and metal natural sources that can contaminate the water reservoirs and consequently become a concern for human health. The present study evaluated the water quality of the Riacho das Cachoeiras Dam located in the urban area of Lajes Pintadas (state of Rio Grande do Norte, Brazil) as source for human consumption. An analysis of Physicochemical parameters, heavy metal content and Radon in water samples was performed along with the assessment of the water mutagenic potential through Micronucleus Test (MN) on Tradescantia pallida and Oreochromis niloticus. The content of metals in water for Al, Cd, and Ni were above water quality guidelines for human consumption. Moreover, high levels of Pb along with dissolved Radon were found. An acute and chronic mutagenic water capability was observed. These findings demonstrated that the water quality is unsuitable for human consumption due to the presence of high levels of contaminants mainly from geogenic origin and its deleterious effect on living systems.

A região semiárida brasileira apresenta condições ambientais adversas para população local, como a escassez na disponibilidade de água e a presença de fontes naturais de radônio e de metais que podem contaminar os reservatórios de água e, consequentemente, tornar-se um problema de saúde humana. O estudo avaliou a qualidade da água do Açude do Riacho das Cachoeiras localizado na área urbana de Lajes Pintadas (Rio Grande do Norte, Brasil) como fonte para o consumo humano. Foram realizadas análises físico-químicas, de conteúdo de metais e de radônio em amostras de água em conjunto com a avaliação do potencial mutagênico da água por meio do teste de micronúcleos (MN) em Tradescantia pallida e Oreochromis niloticus. Os metais Al, Cd, e Ni estavam acima das diretrizes de qualidade da água para o consumo humano. Além disso, foram encontrados altos níveis de Pb dissolvido, juntamente com o radônio. Observou -se um potencial de indução de efeito mutagênico nas amostras de água testadas, tanto na exposição aguda quanto na crônica. Estes resultados demonstram que a qualidade da água do Açude está imprópria para o consumo humano devido à presença de elevados níveis de contaminantes de origem geogênica, com capacidade de exercer efeito deletério sobre os organismos.

Validation of Comet assay in Oregon-R and Wild type strains of Drosophila melanogaster exposed to a natural radioactive environment in Brazilian semiarid region.

Natural radiation of geological origin is a common phenomenon in Brazil, a country where radioactive agents such as uranium may be often found. As an unstable atom, uranium undergoes radioactive decay with the generation of a series of decay by-products, including radon, which may be highly genotoxic and trigger several pathological processes, among which cancer. Because it is a gas, radon may move freely between cracks and gaps in the ground, seeping upwards into the buildings and in the environment. In this study, two Drosophila melanogaster Meigen (Diptera, Drosophilidae) strains called Oregon-R and Wild (collected in a non-radioactive environment) were exposed to atmospheric radiation in the Lajes Pintadas city, in the semiarid zone of northeastern Brazil. After six days of environmental exposure, the organisms presented genetic damage significantly higher than that of the negative control group. The genotoxic effects observed reinforce the findings of other studies carried out in the same region, which warn about the environmental risks related to natural radioactivity occurrence. The results also validate the use of the Comet assay in hemocytes of D. melanogaster as a sensitive test to detect genotoxicity caused by natural radiation, and the use of a recently collected D. melanogaster strain in the environmental of radon.

Mutagenic potential assessment associated with human exposure to natural radioactivity.

Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m-3. The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality.