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Supplementary Methods and Materials, Figures 1-4 from Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis

Breast cancer is the leading cause of cancer-related death in women worldwide. Several studies have addressed the association between cancer in humans and agricultural pesticide exposure. Evidence indicates that exposure to organophosphorous pesticides such as parathion and malathion occurs as a result of occupational factors since they are extensively used to control insects. On the other hand, estrogens have been considered beneficial to the organism; however, epidemiological studies have pointed out an increased breast cancer risk in both humans and animals. Experimental female rat mammary gland cancer models were developed after exposure to parathion, malathion, eserine, an acetylcholinesterase inhibitor, and estrogen allowing the analysis of the signs of carcinogenicity as alteration of cell proliferation, receptor expression, genomic instability, and cell metabolism in vivo and in vitro. Thus, pesticides increased proliferative ducts followed by ductal carcinoma; and 17β-estradiol increased proliferative lobules followed by lobular carcinomas. The combination of both pesticides and either eserine or estrogen induced tumors with both types of structures followed by mammary gland tumors and metastasis to the lung and kidneys after 240 days of a 5-day treatment. Studies also showed that these pesticides and eserine decreased three to five times the acetylcholinesterase activity in the serum compared to controls whereas terminal end buds increased in number, being inhibited by atropine. Genomic instability was analyzed in such tissues (mp53, CYP1A2, c-myc, c-fos, ERα, M2R) and pesticides increased protein expression that was stimulated by estrogens but inhibited by atropine. Eserine also transformed the epithelium of the rat mammary gland in the presence of estrogen and increased the number of terminal end buds after treatment inducing mammary carcinomas. Then, enzymatic digestion of such structures gave rise to cells with increased DNA synthesis and induced anchorage independence. Thus, there were changes in the epithelium of the mammary gland influencing breast carcinogenesis. Furthermore, these substances and acetylcholine also showed the signs of carcinogenicity in vitro as cell proliferation, receptor expression (ERα, ErbB2, M2R), genomic instability (c-myc, mp53, ERα, M2R), and cell metabolism. A unique cellular model is also presented here based on the use of MCF-10 F, a non-tumorigenic cell line that represents a valuable clinically translatable experimental approach that identifies mechanistic links for pesticides and estrogen as suspect human carcinogenic agents.

Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line, MCF-10F, to low doses of high linear energy transfer (LET) α particle radiation (150 keV/μm) and subsequent growth in the presence or absence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation after being irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles. In the present report, the profiling of differentially expressed genes associated with growth factors was analyzed in their relationship with clinical parameters. Thus, the results indicated that Fibroblast growth factor2 gene expression levels were higher in cells transformed by radiation or in the presence of ionizing radiation; whereas the fibroblast growth factor-binding protein 1gene expression was higher in the tumor cell line derived from this model. Such expressions were coincident with higher values in normal than malignant tissues and with estrogen receptor (ER) negative samples for both gene types. The results also showed that transforming growth factor alpha gene expression was higher in the tumor cell line than the tumorigenic A5 and the transformed A3 cell line, whereas the transforming growth factor beta receptor 3 gene expression was higher in A3 and A5 than in Tumor2 cell lines and the untreated controls and the E cell lines. Such gene expression was accompanied by results indicating negative and positive receptors for transforming growth factor alpha and the transforming growth factor beta receptor 3, respectively. Such expressions were low in malignant tissues when compared with benign ones. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expressions were found to be present in all BRCA patients that are BRCA-Basal, BRCA-LumA, and BRCA-LumB, except in BRCA-Her2 patients. The results also indicated that the insulin growth factor receptor gene expression was higher in the tumor cell line Tumor2 than in Alpha3 cells transformed by ionizing radiation only; then, the insulin growth factor receptor was higher in the A5 than E cell line. The insulin growth factor receptor gene expression was higher in breast cancer than in normal tissues in breast cancer patients. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expression levels were in stages 3 and 4 of breast cancer patients. It can be concluded that, by using gene technology and molecular information, it is possible to improve therapy and reduce the side effects of therapeutic radiation use. Knowing the different genes involved in breast cancer will make possible the improvement of clinical chemotherapy.

BACKGROUND: Multiple epidemiological studies have shown that exposure to pesticides is associated with adverse health outcomes. However, the literature on pesticide-related health effects in the Latin American and the Caribbean (LAC) region, an area of intensive agricultural and residential pesticide use, is sparse. We conducted a scoping review to describe the current state of research on the health effects of pesticide exposure in LAC populations with the goal of identifying knowledge gaps and research capacity building needs. METHODS: We searched PubMed and SciELO for epidemiological studies on pesticide exposure and human health in LAC populations published between January 2007 and December 2021. We identified 233 publications from 16 countries that met our inclusion criteria and grouped them by health outcome (genotoxicity, neurobehavioral outcomes, placental outcomes and teratogenicity, cancer, thyroid function, reproductive outcomes, birth outcomes and child growth, and others). RESULTS: Most published studies were conducted in Brazil (37%, n = 88) and Mexico (20%, n = 46), were cross-sectional in design (72%, n = 167), and focused on farmworkers (45%, n = 105) or children (21%, n = 48). The most frequently studied health effects included genotoxicity (24%, n = 62) and neurobehavioral outcomes (21%, n = 54), and organophosphate (OP) pesticides were the most frequently examined (26%, n = 81). Forty-seven percent (n = 112) of the studies relied only on indirect pesticide exposure assessment methods. Exposure to OP pesticides, carbamates, or to multiple pesticide classes was consistently associated with markers of genotoxicity and adverse neurobehavioral outcomes, particularly among children and farmworkers. DISCUSSION: Our scoping review provides some evidence that exposure to pesticides may adversely impact the health of LAC populations, but methodological limitations and inconsistencies undermine the strength of the conclusions. It is critical to increase capacity building, integrate research initiatives, and conduct more rigorous epidemiological studies in the region to address these limitations, better inform public health surveillance systems, and maximize the impact of research on public policies., Fil: Zúñiga-Venegas, Liliana A. Universidad Católica del Maule. Centro de Investigaciones de Estudios Avanzados del Maule; Chile, Fil: Hyland, Carly. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Hyland, Carly. Boise State University. School of Public Health and Population Science; Estados Unidos, Fil: Muñoz-Quezada, María Teresa. Universidad Católica del Maule. Facultad de Ciencias de la Salud. Centro de Investigación en Neuropsicología y Neurociencias Cognitivas; Chile, Fil: Quirós-Alcalá, Lesliam. John Hopkins University. Bloomberg School of Public Health. Department of Environmental Health and Engineering; Estados Unidos, Fil: Quirós-Alcalá, Lesliam. University of Maryland. School of Public Health. Maryland Institute of Applied Environmental Health; Estados Unidos, Fil: Butinof, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina, Fil: Buralli, Rafael. Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Saúde Ambiental; Brasil, Fil: Cardenas, Andres. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Fernandez, Ricardo A. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Foerster, Claudia. Universidad de O’Higgins. Instituto de Ciencias de la Agroalimentarias, Animales y Ambientales; Chile, Fil: Gouveia, Nelson. Universidade de São Paulo. Faculdade de Medicina. Departamento de Medicina Preventiva; Brasil, Fil: Jara, Juan P. Gutiérrez. Universidad Católica del Maule. Centro de Investigaciones de Estudios Avanzados del Maule; Chile, Fil: Lucero, Boris A. Universidad Católica del Maule. Facultad de Ciencias de la Salud. Centro de Investigación en Neuropsicología y Neurociencias Cognitivas; Chile, Fil: Muñoz, María Pía. Universidad de Chile. Facultad de Medicina. Escuela de Salud Pública; Chile, Fil: Ramírez-Santana, Muriel. Universidad Católica del Norte. Facultad de Medicina. Departamento de Salud Pública; Chile, Fil: Smith, Anna R. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Tirado, Noemi. Universidad Mayor de San Andrés. Facultad de Medicina. Instituto de Genética; Bolivia, Fil: de Joode, Berna van Wendel. Universidad Nacional. Central American Institute for Studies on Toxic Substances. Infants’ Environmental Health Study; Costa Rica, Fil: Calaf, Gloria M. Universidad de Tarapacá. Instituto de Alta Investigación; Chile, Fil: Calaf, Gloria M. Columbia University Medical Center; Estados Unidos, Fil: Handal, Alexis J. University of Michigan School of Public Health. Department of Epidemiology; Estados Unidos, Fil: da Silva, Agnes Soares. Pan American Health Organization. Estados Unidos, Fil: Cortés, Sandra. Pontificia Universidad Católica de Chile. Departamento de Salud Pública. Centro de Desarrollo Urbano Sustentable. Centro Avanzado de Enfermedades Crónicas (ACCDiS); Chile, Fil: Mora, Ana M. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Mora, Ana M. Universidad Nacional. Central American Institute for Studies on Toxic Substances. Infants’ Environmental Health Study; Costa Rica

Glyphosate, the active ingredient in several broad-spectrum herbicide formulations, has been validated and widely used throughout the world. Recent reports have questioned its safety, showing that glyphosate may act as an endocrine disruptor by promoting estrogenic activity. However, the molecular mechanism involved in this phenomenon remains unclear. Therefore, here we aimed to elucidate the mechanism by which glyphosate induces estrogenic activity using estrogen-sensitive breast cancer cell line models. Our results show that glyphosate mimics the cell effects of 17β-estradiol (E2), promoting estrogen receptor α (ERα) phosphorylation, its degradation, and transcriptional activity at high concentrations. The molecular mechanism seems involved in the ERα ligand-binding domain (LBD). Molecular simulations suggest a plausible interaction between glyphosate and the LBD through a coordinated complex involving divalent cations such as Zn (II). In addition, glyphosate exposure alters the level of Cyclin-dependent kinase 7 that contribute to ERα phosphorylation. Finally, glyphosate increases cell proliferation rate and levels of cell cycle regulators, accompanied by an increase in anchorage-independent growth capacity. These findings suggest that glyphosate at high concentrations, induces estrogen-like effects through an ERα ligand binding site-dependent mechanism, leading to cellular responses resulting from a complex interplay of genomic and non-genomic events.

Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, lung, gastric, colon, pancreatic, ovarian, prostate, and brain cancer. This work aimed to study the correlation between epidermal growth factor receptors and cholinergic muscarinic receptors, the survival differences adjusted by the stage clinical factor, and the association between gene expression and immune infiltration level in breast, lung, stomach, colon, liver, prostate, and glioblastoma human cancers. Thus, targeting cholinergic muscarinic receptors appears to be an attractive therapeutic alternative due to the complex signaling pathways involved.

Turbulent secondary flows are defined as Prandtl's secondary flow of the first or second kind, the former produced by stretching and/or tilting of vorticity, the latter produced via spatial heterogeneity of Reynolds stresses. Both mechanisms are instantaneously active within inertia-dominated wall turbulence; Reynolds stress spatial heterogeneity is required for Reynolds-averaged secondary flows. Spanwise-variable surface roughness can induce turbulent stress spatial heterogeneity in the spanwise–wall-normal plane and provide sustenance for streamwise-aligned mean secondary flows. Herein, we demonstrate that turbulent secondary flows can also be sustained by spanwise variability in the surface heat flux in unstably stratified turbulent channels, defined hereafter as Prandtl's secondary flow of the third kind. Support for this mechanism is established with scaling arguments, while large-eddy simulation is used to model inertia-dominated channel turbulence responding to a lower boundary with uniform aerodynamic/hydrodynamic roughness but spanwise-variable surface heat flux. Transport equations for streamwise vorticity and turbulent kinetic energy, $k$ , outline the conditions needed for third-kind production: shear and buoyancy production over the elevated heat flux regions necessitates lateral entrainment of low- $k$ fluid, inducing mean counter-rotating secondary cells aligned such that upwelling and downwelling occur over the high and low heat flux regions, respectively. Buoyancy-driven production of $k$ alters aggregate flow response and thus is a distinctly different mechanism responsible for sustenance of secondary flows.

The complete evaluation of the carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy will be published in Volume 131 of the IARC Monographs., [Excerpt] In March, 2022, a Working Group of 31 scientists from 13 countries met remotely at the invitation of the International Agency for Research on Cancer (IARC) to finalise their evaluation of the carcinogenicity of nine agents: cobalt metal (without tungsten carbide or other metal alloys), soluble cobalt(II) salts, cobalt(II) oxide, cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, trivalent antimony, pentavalent antimony, and weapons-grade tungsten (with nickel and cobalt) alloy. For cobalt metal and the cobalt compounds, particles of all sizes were included in the evaluation. These assessments will be published in Volume 131 of the IARC Monographs.1 Cobalt metal and soluble cobalt(II) salts were classified as “probably carcinogenic to humans” (Group 2A) based on “sufficient” evidence for cancer in experimental animals and “strong” mechanistic evidence in human primary cells. Cobalt(II) oxide and weapons-grade tungsten alloy were classified as “possibly carcinogenic to humans” (Group 2B) based on “sufficient” evidence in experimental animals. Trivalent antimony was classified as “probably carcinogenic to humans” (Group 2A), based on “limited” evidence for cancer in humans, “sufficient” evidence for cancer in experimental animals, and “strong” mechanistic evidence in human primary cells and in experimental systems. Cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, and pentavalent antimony were each evaluated as “not classifiable as to its carcinogenicity to humans” (Group 3).[...]

Breast cancer (BC) is the most common cancer among women worldwide. BRCA1/2 are responsible for 16–20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia Complementation Group M (FANCM) being one of these. Two variants in FANCM, rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNPs were genotyped in 492 BRCA1/2-negative BC cases and 673 controls. Our data do not support an association between FANCM rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of FANCM mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in BRCA1/2-negatives and for early-onset non-familial BC in Chilean BC cases.

Lung cancer (LC) is the leading cause of cancer death worldwide. Tobacco smoke is the most frequent risk factor etiologically associated with LC, although exposures to other environmental factors such as arsenic, radon or asbestos are also involved. Additionally, the involvement of some viral infections such as high-risk human papillomaviruses (HR-HPVs), Merkel cell polyomavirus (MCPyV), Jaagsiekte Sheep Retrovirus (JSRV), John Cunningham Virus (JCV), and Epstein–Barr virus (EBV) has been suggested in LC, though an etiological relationship has not yet been established. EBV is a ubiquitous gamma herpesvirus causing persistent infections and some lymphoid and epithelial tumors. Since EBV is heterogeneously detected in LCs from different parts of the world, in this review we address the epidemiological and experimental evidence of a potential role of EBV. Considering this evidence, we propose mechanisms potentially involved in EBV-associated lung carcinogenesis. Additional studies are warranted to dissect the role of EBV in this very frequent malignancy.

Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell–cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.

Simple Summary The present work analyzed the expression of genes involved in radiation, using an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Results showed important findings of genes involved in cancers of the breast, lung, and nervous system, and others. Most of those genes analyzed in these studies such as ATM, selenoproteins, GABA receptor, interleukins, epsin, and cathepsin inhibitors like stefins, and metallothioneins can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. In conclusion, gene signature demonstrated to be specific to cell line types, hence cell-dependency must be considered in future radiotherapy treatment planning since molecular and clinical features affect such results. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects. Abstract This study aimed to analyze the expression of genes involved in radiation, using an Affymetrix system with an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Altered expression of different molecules was detected in the non-tumorigenic Alpha3, a malignant cell line transformed only by radiation and originally derived from the parental MCF-10F human cell line; that was compared with the Alpha 5 cell line, another cell line exposed to radiation and subsequently grown in the presence 17β-estradiol. This Alpha5, a tumorigenic cell line, originated the Tumor2 cell line. It can be summarized that the Alpha 3 cell line was characterized by greater gene expression of ATM and IL7R than control, Alpha5, and Tumor2 cell lines, it presented higher selenoprotein gene expression than control and Tumor2; epsin 3 gene expression was higher than control; stefin A gene expression was higher than Alpha5; and metallothionein was higher than control and Tumor2 cell line. Therefore, radiation, independently of estrogen, induced increased ATM, IL7R, selenoprotein, GABA receptor, epsin, stefin, and metallothioneins gene expression in comparison with the control. Results showed important findings of genes involved in cancers of the breast, lung, nervous system, and others. Most genes analyzed in these studies can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. Most of all, it was revealed that in the Alpha model, a breast cancer model developed by the authors, the cell line transformed only by radiation, independently of estrogen, was characterized by greater gene expression than other cell lines. Understanding the effect of radiotherapy in different cells will help us improve the clinical outcome of radiotherapies. Thus, gene signature has been demonstrated to be specific to tumor types, hence cell-dependency must be considered in future treatment planning. Molecular and clinical features affect the results of radiotherapy. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects while providing new insights into breast cancer-related fields.

Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several products used in daily activities. Once in the organism, they can disrupt the endocrine function by mimicking or blocking naturally occurring hormones due to their similar chemical structure. This endocrine disruption is the most important cause of the well‑known hormone‑associate types of cancer. Additionally, it is decisive to determine the susceptibility of each organ to these compounds. Therefore, the present review aimed to summarize the effect of different environmental substances such as bisphenol A, dichlorodiphenyltrichloroethane and polychlorinated biphenyls in both the mammary and the prostate tissues. These organs were chosen due to their association with the hormonal system and their common features in carcinogenic mechanisms. Outcomes derived from the present review may provide evidence that should be considered in future debates regarding the effects of endocrine disruptors on carcinogenesis.

Breast cancer is the most frequently diagnosed malignancy in women in the western world. Oxidative stress is one of the important pathogenic factors of cancer development. Among the antioxidants, curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane) is a dietary natural yellow pigment derived from the rhizome of the herb Curcuma longa (Zingiberaceae). This study evaluated the effects of curcumin on oxidative stress in an established in vitro experimental breast cancer model (Alpha-model) as well as in isolated cells derived from breast specimens. Such model was developed with the immortalized breast cell line, MCF-10F, that was exposed to low doses of high linear energy transfer (LET) α particles (150 keV/μm) of radiation, values comparable to α particles emitted by radon progeny, and cultured in the presence of 17β-estradiol. It consisted of cell lines in different stages of transformation: (i) MCF-10F, (ii) an estrogen-treated, called Estrogen, (iii) a malignant one, called Alpha3, (iv) a malignant and tumorigenic one, called Alpha5, and (v) a tumor cell line, called Tumor2 derived from a tumor after injection of previous one in nude mice. Free radical production is ubiquitous in all organisms and it is enhanced in many diseases. Curcumin interferes with multiple genes that promote carcinogenesis, thereby affecting genomic instability. Alteration in protein expressions involved in key signaling pathways and epithelial-mesenchymal transition render this model an important tool for monitoring effects of natural dietary compounds in breast carcinogenesis.

Pirin is an oxidative stress (OS) sensor belonging to the functionally diverse cupin superfamily of proteins. Pirin is a suggested quercetinase and transcriptional activator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Its biological role in cancer development remains as a novel area of study. This review shows accumulating evidence on the contribution of Pirin in epithelial cancers, signaling pathways involved, and as a suggested therapeutic target. Finally, we propose a model in which Pirin is upregulated by physical, chemical or biological factors involved in OS and cancer development.

Cancer development is a multistep process that may be induced by a variety of compounds. Environmental substances, such as pesticides, have been associated with different human diseases. Organophosphorus pesticides (OPs) are among the most commonly used insecticides. Despite the fact that organophosphorus has been associated with an increased risk of cancer, particularly hormone‑mediated cancer, few prospective studies have examined the use of individual insecticides. Reported results have demonstrated that OPs and estrogen induce a cascade of events indicative of the transformation of human breast epithelial cells. In vitro studies analyzing an immortalized non‑tumorigenic human breast epithelial cell line may provide us with an approach to analyzing cell transformation under the effects of OPs in the presence of estrogen. The results suggested hormone‑mediated effects of these insecticides on the risk of cancer among women. It can be concluded that, through experimental models, the initiation of cancer can be studied by analyzing the steps that transform normal breast cells to malignant ones through certain substances, such as pesticides and estrogen. Such substances cause genomic instability, and therefore tumor formation in the animal, and signs of carcinogenesis in vitro. Cancer initiation has been associated with an increase in genomic instability, indicated by the inactivation of tumor‑suppressor genes and activation of oncogenes in the presence of malathion, parathion, and estrogen. In the present study, a comprehensive summary of the impact of OPs in human and rat breast cancer, specifically their effects on the cell cycle, signaling pathways linked to epidermal growth factor, drug metabolism, and genomic instability in an MCF‑10F estrogen receptor‑negative breast cell line is provided.

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

Evaluation of carcinogenic substances from the environment is a challenge for scientists. Recently, a novel approach based on 10 key characteristics of human carcinogens classified by the International Agency for Research on Cancer (IARC) has emerged. Carcinogenesis depends on different mechanisms and factors, including genetic, infectious (bacteria, viruses) and environmental (chemicals) factors. Endocrine disruptors are exogenous chemicals that can interfere and impair the function of the endocrine system due to their interaction with estrogen receptors or their estrogen signaling pathways inducing adverse effects in the normal mammary development, originating cancer. They are heterogeneous chemicals and include numerous synthetic substances used worldwide in agriculture, industry and consumer products. The most common are plasticizers, such as bisphenol A (BPA), pesticides, such as dichlorodiphenyltrichloroethane, and polychlorinated biphenyls (PCBs). Xenoestrogens appear to serve an important role in the increased incidence of breast cancer in the United States and numerous other countries. Several studies have demonstrated the role of organochlorine xenoestrogens in breast cancer. Therefore, the overall cumulative exposure of women to estrogens results in an increased risk for this type of cancer. Factors like lifestyle and diet also serve a role in the increased incidence of this disease. The aim of the present study was to analyze these chemical compounds based on the key characteristics given by the IARC, with a special focus on breast cancer, to establish whether these compounds are carcinogens, and to create a model for future analysis of other endocrine disruptors.

Breast, cervical and ovarian cancers are highly prevalent in women worldwide. Environmental, hormonal and viral-related factors are especially relevant in the development of these tumors. These factors are strongly related to oxidative stress (OS) through the generation of reactive oxygen species (ROS). The OS is caused by an imbalance in the redox status of the organism and is literally defined as "an imbalance between ROS generation and its detoxification by biological system leading to impairment of damage repair by cell/tissue". The multistep progression of cancer suggests that OS is involved in cancer initiation, promotion and progression. In this review, we described the role of OS and the interplay with environmental, host and viral factors related to breast, cervical and ovarian cancers initiation, promotion and progression. In addition, the role of the natural antioxidant compound curcumin and other compounds for breast, cervical and ovarian cancers prevention/treatment is discussed.

Breast cancer remains the second most common disease worldwide. Radiotherapy, alone or in combination with chemotherapy, is widely used after surgery as a treatment for cancer with proven therapeutic efficacy manifested by reduced incidence of loco-regional and distant recurrences. However, clinical evidence indicates that relapses occurring after radiotherapy are associated with increased metastatic potential and poor prognosis in the breast. Among the anticarcinogenic and antiproliferative agents, curcumin is a well-known major dietary natural yellow pigment derived from the rhizome of the herb Curcuma longa (Zingiberaceae). The aim of the present study was to analyze the differential expression of metastatic genes in radiation- and estrogen-induced breast cancer cell model and the effect of curcumin on such metastatic genes in breast carcinogenesis. Expression levels of TGF-α and TGFβ1 genes were upregulated in MCF-10F and downregulated in Tumor2 cell lines treated with curcumin. Expression levels of other genes such as caspase 9 and collagen 4 A2 were upregulated in both MCF-10F and Tumor2-treated cell lines. Integrin α5 and cathepsin B and D decreased its expression in Tumor2, whereas E-Cadherin, c-myc and CD44 expressions were only increased in MCF-10F. It can be concluded that metastatic genes can be affected by curcumin in cancer progression and such substance can be used in breast cancer patients with advanced disease without side-effects commonly observed with therapeutic drugs.

In this work, we present the maximum daily values of solar ultraviolet A radiation (UV-A) as a function of time. The results indicated that such values reached a maximum of 93.9 W/m2 in 2010 and a minimum of 16.5 W/m2 in 2012. The annual averages of both UV-A and solar ultraviolet B radiation (UV-B) from 2007 to 2013 were recorded. UV-A was always higher than UV-B. However, UV-B is more energetic due to its intrinsic wavelength. The nonmelanoma skin cancer mortality incidences per 100,000 inhabitants in Arica and in Chile as a function of time between 2007 and 2013 indicated that these mortality rates varied from 3.12 (Arica) to 0.88 (Chile) in 2007 and 2.71 (Arica) to 0.88 (Chile) in 2013. The nonmelanoma skin cancer prevalence rates per 100,000 inhabitants in Arica were 22.2 in 2007 and 19.5 in 2013. The relationship between NMSC and exposure to UV-A is given. In Arica, we report high levels of UV-A and the highest NMSC rates compared with other regions in our country.

Breast cancer is the most prevalent type of cancer among women worldwide and it is characterized by a high morbidity. Curcumin is a naturally occurring compound derived from the rhizome of Curcuma longa and is known to have antioxidant and anticarcinogenic properties. Emerging evidence has indicated that microRNAs (miRNAs or miRs) function as oncogenes or tumor suppressor genes to control invasion and migration. The aim of this study was to evaluate the effects of curcumin on genes implicated in epithelial‑mesenchymal transition (EMT) and to examine the involvement of Rho‑A in the migration and invasion of MCF‑10F and MDA‑MB‑231 breast cell lines. Furthermore, to the best of our knowledge, this is the first study to examine the effects of curcumin on Rho‑A and on genes involved in EMT, such as Axl, Slug and CD24 in order to determine whether the compound is able to prevent migration and invasion by targeting miRNAs as a regulator of such genes. Specifically, we focused on miR‑34a which acts as a tumor suppressor gene in human breast cell lines. The present study demonstrated that the Axl, Slug and CD24 genes were implicated in EMT, and Rho‑A was also involved in the migration and invasion of MCF‑10F and MDA‑MB‑231 cell lines. Curcumin also acted upon the miRNA as a regulator of genes implicated in EMT and upon Rho‑A as well, affecting the migration and invasion of the cells. This occurred independently of their estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) receptors in the non‑malignant MCF‑10F and malignant MDA‑MB‑231 breast cell lines, which are both negative for such receptors.

Hematologic diseases are a heterogeneous group of malignancies that affect people worldwide such as leukemia, lymphoma and multiple myelomas. The aim of this study was to characterize the frequency of hematological diseases in the population of Arica, Chile (18°S, 70°W), between 2011 and 2014. A total of 108 cases of hematologic malignancies were registered at Dr. Juan Noe Crevani Regional Hospital in this period; 40 male and 52 female cases were included in this retrospective and descriptive analysis. The overall median age at diagnosis for hematological malignancies was 59 years (range, 17 to 96 years). The results indicated that the frequency of hematological diseases such as non-Hodgkin lymphoma and leukemia was not associated with sex, ethnicity and type of disease. However, in 2012 there was an increased number of cases of Hodgkin lymphoma compared with any other year in the study, whereas the number of multiple myeloma cases decreased between 2011 and 2014. No significant differences were observed among different types of disease, nor among the types of leukemia. However, when intervals of age were considered, it was revealed that patients >75 years had the highest incidence of hematological malignancies, mainly multiple myeloma, compared with other age groups. However, young adults were more commonly diagnosed with Hodgkin lymphoma than other disease types. A non-significant difference was observed in leukemia between 2011 and 2014 when sex was taken into consideration, in which the incidence rate was higher in females compared with males. Hodgkin lymphoma was most commonly at stage II and non-Hodgkin lymphoma was most commonly at stage IV. No significant differences were observed between the nodal and extranodal type, mixed cellularity and nodular sclerosis or in the morphology of non-Hodgkin lymphoma cell type. Overall, there was a decrease in the frequency of hematological malignancies between 2011 and 2014, but no significant differences were observed in males or females. This study provided for the first time the pattern and distribution of hematological diseases in Arica, Chile.

Glyphosate is a large-spectrum herbicide that was introduced on the market in 1974. Due to its important impact on the crop industry, it has been significantly diversified and expanded being considered the most successful herbicide in history. Currently, its massive use has led to a wide environmental diffusion and its human consumption through food products has made possible to detect it in urine, serum, and breast milk samples. Nevertheless, recent studies have questioned its safety and international agencies have conflicting opinions about its effects on human health, mainly as an endocrine-disrupting chemical (EDC) and its carcinogenic capacity. Here, we conduct a comprehensive review where we describe the most important findings of the glyphosate effects in the endocrine system and asses the mechanistic evidence to classify it as an EDC. We use as guideline the ten key characteristics (KCs) of EDC proposed in the expert consensus statement published in 2020 (La Merrill et al., 2020) and discuss the scopes of some epidemiological studies for the evaluation of glyphosate as possible EDC. We conclude that glyphosate satisfies at least 8 KCs of an EDC, however, prospective cohort studies are still needed to elucidate the real effects in the human endocrine system.