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Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation.
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INTRODUCTION: Preterm newborns struggle with maintaining an adequate respiratory pattern; early caffeine administration is suggested to stimulate respiration and reduce bronchopulmonary dysplasia, however, its consequences on the immature cerebellum remains unknown. This study aimed to assess the impact of early caffeine administration, at standard and high doses, accompanied by supplemental oxygen on cerebellar development in an experimental model. METHODS: Five groups of Wistar pups were formed (n = 8 offspring/group): (a) negative control: no intervention; (b) placebo: pups remaining from birth until the 7th day of life (DOL) exposed to fractional inspired oxygen (FiO2) 45%, resembling preterm infant condition and as a placebo, 0.2 mL oral 5% dextrose, from the first DOL until the 14th DOL; (c) caffeine group: oral caffeine, 1st DOL 20 mg/kg, and from 2nd to 14th DOL, 5 mg/kg (standard dose); (d) caffeine at the standard dose, plus O2: during the first 7 DOLs (FiO2: 45%); (e) caffeine: 40 mg/kg in the first DOL, 10 mg/kg the next 14 DOLs, plus O2 in the first 7 DOLs (FiO2: 45%). Subjects were sacrificed on their 15th DOL; measurements were taken from the cerebellum, specifically the external granular layer (EGL) and molecular layer (ML), with quantification of cell migration. RESULTS: Caffeine administration in pups resulted in a delay in cerebellum development based on persistent transitional EGL cells; this finding was exacerbated in groups exposed to caffeine plus O2, as evident from the thicker EGL. The negative control group showed near-complete cell migration with a thicker ML and a significantly smaller EGL. CONCLUSIONS: Early caffeine administration in newborn rats disrupts cerebellar cortex cell processes and connectivity pathways, with exacerbated effects in groups receiving caffeine plus O2.
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The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.
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BACKGROUND: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. METHODS: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. RESULTS: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). CONCLUSION: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.
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Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.
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Drogas Ilícitas , Trastornos Relacionados con Sustancias , Humanos , Pruebas de Micronúcleos/métodos , Núcleo Celular , Muerte Celular , Nicotiana , Drogas Ilícitas/toxicidad , Mucosa BucalRESUMEN
PURPOSE: Association between variants rs1047972 and rs8173 of the AURKA gene in healthy women and breast cancer (BC) in a Mexican population. METHODS: Genomic DNA samples from 409 healthy women and 572 patients with BC were analyzed for variants rs1047972 and rs8173 of the AURKA gene by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: TT genotype (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.22-5.11; p = 0.0015) and the T allele (OR, 1.16; 95% CI, 1.23-2.12; p = 0.0007) of the rs1047972 variant were associated as risk susceptibility for BC relative to the control group. Contrarily, the GG genotype (OR, 0.64; 95% CI, 0.43-0.94; p = 0.029) was associated as a protective factor of susceptibility of BC of the variant rs8173 of the AURKA gene. Differences were observed in the patients with BC who were carriers of the CT genotype of the rs1047972 variant with overweight, obesity, estrogen receptor-positive plus obesity, Ki-67 (≥ 20%) plus history familial positive of cancer; and for variant rs8173 the BC patients who were CG carriers and presented chemotherapy gastric toxicity, hormonal receptor positive plus chemotherapy gastric toxicity, and menopause status plus chemotherapy gastric toxicity (p < 0.05). Two common haplotypes were identified in the study groups: CG and TC genotypes, were associated as a protective and risk factor, respectively (p < 0.05). CONCLUSION: Variants rs1047972 and rs8173 of the AURKA gene and the TC haplotype were associated as risk susceptibility factors for BC in this population.
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Colorectal cancer (CRC) is a major global health challenge and one of the top 10 cancers in Mexico. Lifestyle and genetic factors influence CRC development, prognosis, and therapeutic response; identifying risk factors, such as the genes involved, is critical to understanding its behavior, mechanisms, and prognosis. The association between KRAS gene variants (rs8720 and rs12587) and CRC in the Mexican population was analyzed. We performed in silico analysis and analyzed 310 healthy individuals and 385 CRC patients using TaqMan assays and real-time PCR. The CC and GG genotypes of rs8720 and rs12587 were identified as CRC risk factors (p < 0.05). The CC and TC genotypes of the rs8720 were associated with rectal cancer, age over 50 years, moderately differentiated histology, and advanced cancer stage. TG and GG genotypes of the rs12587 variant were a risk factor in the CRC group, in patients with stage I-II, males, and stage III-IV non-chemotherapy response. The TG haplotype is protected against CRC. The combined CCGG genotype was linked to CRC risk. In silico analysis revealed that the rs12587 and rs8720 variants could influence KRAS gene regulation via miRNAs. In conclusion, rs8720 and rs12587 variants of the KRAS gene were associated with CRC risk and could influence KRAS regulation via miRNAs.
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Neoplasias Colorrectales , MicroARNs , Masculino , Humanos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas p21(ras)/genética , Predisposición Genética a la Enfermedad , Neoplasias Colorrectales/patología , México , Polimorfismo de Nucleótido Simple/genética , MicroARNs/genéticaRESUMEN
Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.
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This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas Experimentales , Neoplasias Hepáticas , Ratas , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Ratas Wistar , Hígado/metabolismo , 2-Acetilaminofluoreno/toxicidad , Dietilnitrosamina/toxicidad , alfa-Fetoproteínas , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/patologíaRESUMEN
Annona muricata have been extensively used in traditional medicine to treat multiple diseases, including cancers. This study evaluated the genotoxic potential and antigenotoxic activities of A. muricata aqueous and ethanolic leaf extracts by employing an in vivo erythrocyte rodent micronucleus assay. Different doses (187.5, 375, and 750 mg/kg) of both extracts were administered orally for 5 days alone and combined with cyclophosphamide (CP, 60 mg/kg) to BALB/c mice. Also, it was administered orally to Wistar rats for 5 days through the final stage of gestation. No genotoxic or cytotoxic effects were observed in the two adult rodent models when A. muricata was administered orally nor in newborn rats transplacentally exposed to the extracts. Moreover, A. muricata aqueous and ethanolic leaf extracts demonstrated a protective effect against CP-induced DNA damage. Due to its lack of genotoxic effect and its capacity to decrease DNA damage, A. muricata is likely to open an interest field regarding its potential safe use in clinical applications.
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Annona , Extractos Vegetales , Ratones , Ratas , Animales , Extractos Vegetales/uso terapéutico , Roedores , Ratas Wistar , Pruebas de Micronúcleos , Eritrocitos , Daño del ADN , Hojas de la PlantaRESUMEN
The superoxide dismutase (SOD) is the principal antioxidant defense system in the body that is activated by a reactive oxygen species. Some variants of the SOD2 gene have been associated with cancer. The rs4880 variant was determined by PCR real-time and the rs5746136 variant by PCR-RFLP in healthy subjects and in breast cancer (BC) patients. The rs4880 and rs5746136 variants were associated with BC susceptibility when BC patients and the control group were compared for the CT, TT, CTCC, and the T alleles (p < 0.05). The CT genotype of the rs4880 variant showed significant statistical differences in patients and controls aged ≤ 45 years old, and with hormonal consumption (p < 0.05). The rs4880 variant was associated with BC patients with CTTT genotype and obesity, the presence of DM2-SAH, and a non-chemotherapy response (p < 0.05). Additionally, the rs5746136 variant was associated with susceptibility to BC with Ki-67 (≥20%), luminal A type BC, and a chemotherapy partial response (p < 0.05) in BC patients who carry TT, TC, and CTTT genotypes, respectively. The haplotype T/T (OR 1.98; 95% CI 1.20−3.26, p = 0.005) was observed to be a risk factor for BC. The rs4880 and rs5746136 variants in the SOD2 gene were associated with BC susceptibility.
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Background: Variants of the estrogen receptor b (ESR2) gene have been associated with different types of cancer. However, these associations have been inconsistent. We genotyped the ESR2 variants (rs1256049, rs4986938, and rs1256030) in breast cancer (BC) patients and in healthy women. Results: The variants rs1256049 and rs4986938 in the ESR2 gene were not associated with risk susceptibility in BC patients. However, the rs1256030 variant had an association as a risk factor for BC patients when compared with controls and BC patients for the TT genotype (odds ratio (OR) 1.86, 95% confidence intervals (CI) [1.05-3.28], p = 0.042). In addition, differences were observed in patients and controls carrying the TT genotype under 50 years of age (OR 1.85, 95% CI [1.05-3.27], p = 0.043). Thus, evident differences showed the rs1256030 variant in patients with TT, TC, and TC+TT genotypes with: (1) Stage IV (OR 1.60, 95% CI [1.06-2.54], p = 0.033), and (2) Luminal A (OR 1.60, 95% CI [0.47-0.21], p = 0.041), as well as in BC carriers of the TT genotype with indices of cellular proliferative (Ki-67) elevated (>20%) and overweight (OR 1.67, 95% CI [0.85-3.28], p = 0.041), respectively. In BC HER2 with lymph node metastasis, the TT genotype was a protective factor (OR 0.38, 95% CI [0.18-0.78], p = 0.005). The identification of haplotypes included two common GAT as risk factors (OR 3.1, 95% CI [1.31-7.72], p = 0.011) and GGC as a protective factor (OR 0.7, 95% CI [0.60-0.97], p = 0.034). The haplogenotype GGGATC was a risk factor (OR 2.5, 95% CI [1.28-5.0], p = 0.008). Conclusion: The variant rs1256030 (TT) of the ESR2 gene and haplotype GAT were associated with susceptibility to BC as risk factors in this sample from the Mexican population.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Receptor beta de Estrógeno/genética , Factores de RiesgoRESUMEN
Micronuclei (MN) are used to assess genotoxic exposure, whereas nuclear buds (NBs) have been linked to genotoxic events. Crocodylus moreletii was studied to identify MN and NBs. Three groups were formed: Group 1 (water) and groups 2 and 3 (7 or 10 mg/kg of cyclophosphamide). A drop of blood was obtained daily from the claw tip at 0 to 120 h. Spontaneous micronucleated erythrocytes (MNEs) and erythrocytes with nuclear buds (NBEs) were counted. The frequencies of micronucleated young erythrocytes (MNYEs) and NB young erythrocytes (NBYEs) were evaluated, including the ratio of young erythrocytes (YE)/1000 total erythrocytes. No significant differences were observed in the YE proportion on sampling days; group 1 did not show differences for any parameter, whereas group 2 showed significant differences in MNEs and NBEs, and group 3 showed differences in NBEs and NBYEs. Some mitotic activity in circulation was observed in YEs. In conclusion, NBEs could be a more sensitive biomarker to genotoxic damage than MNEs. The identification of these biomarkers leads us to propose Crocodylus moreletii as a possible environment bioindicator because these parameters could be useful to analyze the in vivo health status of these reptiles and for biomonitoring genotoxic pollutants in their habitats.
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The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.
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Inestabilidad Genómica , Infecciones por VIH/genética , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Relación CD4-CD8 , Femenino , Inestabilidad Genómica/efectos de los fármacos , VIH/efectos de los fármacos , VIH/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral/efectos de los fármacos , Carga Viral/fisiología , Adulto JovenRESUMEN
Air pollution has become a serious public health problem globally. Recent studies support the harmful effect of air pollution on human health, in addition to scientific evidence that recognizes it as a human carcinogen. The buccal micronucleus cytome (BMC) assay is employed extensively to measure cytotoxic and genotoxic damage in a population exposed to environmental contamination. The objective of this study was to evaluate the cytotoxic and genotoxic effects in healthy young adults exposed to different levels of air pollution and to identify areas with air pollution rates above the regulatory limits. This study was performed through the BMC assay in oral mucosa samples from 80 healthy young adults from the Guadalajara metropolitan zone. Three highly contaminated areas were taken into account: Tlaquepaque, Miravalle, and Las Pintas. Las Aguilas, a less contaminated area, was used as a reference. The frequencies of nuclear abnormalities in the areas with the highest and lowest levels of air pollution were compared with the Mann-Whitney U test. In addition, an analysis of the concentration of environmental pollutants, particulate matter ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), were carried out in the mentioned areas, in order to identify the events above the regulatory limits in a year period. The results showed that young adults exposed to a higher concentration of pollutants showed higher frequencies of nuclear abnormalities. The individuals from the areas of Tlaquepaque, Miravalle, and Las Pintas showed cytotoxic damage since statistically significant differences were found in the abnormalities of pyknotic nuclei (PNs), condensed chromatin (CC), karyorrhexis (KX), and karyolysis (KL). The individuals who showed the most cytotoxic damage were from the Las Pintas area with higher frequencies in nuclear abnormalities (PNs, CC, KX, and KL) (p < 0.0001). Genotoxic damage was found in individuals from two zones, Miravalle and Las Pintas, with statistically significant differences in the abnormality of nuclear buds (NBUDs) (p < 0.0001). Our results suggest that exposure to high levels of air pollution in healthy young adults has an effect on cellular and nuclear integrity and thus in human health, since areas with higher air pollution showed an increase in cytotoxicity, specifically in early and late markers of cell death (CC, KX, PN, and KL) and genotoxic damage (BUDs).
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Contaminación del Aire/efectos adversos , Pruebas de Micronúcleos/métodos , Adolescente , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Ciudades , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Masculino , México , Mucosa BucalRESUMEN
Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradiated cheese. To determine whether exposing lactating rats to X-rays increases the number of micronucleated erythrocytes (MNEs) in peripheral blood of their unexposed or breastfeeding rat pups, 15 female Wistar rats were divided into three groups: Negative control; Experimental group exposed to X-rays, and group exposed to X-rays plus vitamin C. The mothers of groups 2 and 3 were irradiated for three consecutive days after giving birth, returning them to their respective cages each time to continue lactation. A blood sample was taken from the mothers and pups at 0, 24, and 48 hr. Blood smears were stained with acridine orange to analyze MNEs. In mother rats, the frequency of micronucleated polychromatic erythrocytes (MNPCEs) increased significantly at 24 and 48 hr in both study groups exposed to radiation. Likewise, in rat pups the MNPCE and MNE frequencies increased in both groups with radiation and radiation plus vitamin C at 24 and 48 hr, and a protection from vitamin C was observed. In conclusion, the genotoxic damage produced in rat pups that were lactated by mothers irradiated with X-rays is possibly due to the effect of long-lived reactive species that were formed in the breast milk of female Wistar rats during the irradiation process.
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Daño del ADN/genética , Eritrocitos/efectos de la radiación , Lactancia/efectos de la radiación , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Animales , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/radioterapia , Daño del ADN/efectos de la radiación , Eritrocitos/patología , Femenino , Lactancia/genética , Masculino , Pruebas de Micronúcleos , Madres , Embarazo , Ratas , Ratas Wistar , Rayos X/efectos adversosRESUMEN
SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.
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PURPOSE: The rs712 polymorphism in a let-7 microRNA-binding KRAS gene has been associated with different types of cancer, however these associations have been inconsistent. The purpose of this study was to determine the association between rs712 polymorphism in a let-7 microRNA-binding KRAS gene comparing breast cancer (BC) patients with healthy subjects from Mexican population. METHODS: The genotyping of the rs712 polymorphism was performed by polymerase chain reaction (PCR) in 437 BC patients and 414 healthy women. RESULTS: The observed frequencies of the rs712 polymorphism indicated an associated protective factor for BC in the dominant GT+TT model [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.97, p=0.040). An association between genotype and BC patients was evident in chemotherapy response (allele GT, OR 0.032, 95% CI 0.002-0.505, p=0.014), partial chemotherapy response (genotype GT, OR 0.023, 95% CI 0.001-0.419, p=0.011), and gastric and hematological toxicity (genotype GT, OR 0.115, 95% CI 0.028-0.473, p=0.003), Luminal A BC patients with gastric and hematological toxicity (genotype TT, OR 0.236, 95% CI 0.069-0.805, p=0.021) and tobacco consumption (genotype TT, OR 0.283, 95% CI 0.001-0.802, p=0.037) and Luminal B with metastatic lymph node (genotype GT, OR 0.241, 95% CI 0.093-0.626, p=0.003). CONCLUSION: Polymorphism rs712 in KRAS gene was protective factor associated with susceptibility for BC in this sample from Mexican population.
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Neoplasias de la Mama/genética , Genes ras/genética , MicroARNs/metabolismo , Sitios de Unión , Neoplasias de la Mama/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , México , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
Jatropha dioica is traditionally used owing to its antiviral, antifungal, and antimicrobial properties. But, toxicological information regarding J. dioica root total extract is currently limited. The aim of this work was to evaluate in a rat model, the transplacental genotoxicity effect of J. dioica aqueous root total extract. Three different J. dioica aqueous root total extract doses (60, 100, and 300 mg/kg) were administered orally to Wistar rats during 5 days through the pregnancy term (16-21 days). Pregnant rats were sampled every 24 h during the last 6 days of gestation, and pubs were sampled at birth. Genome damage in dams and their newborn pups transplacentally exposed to J. dioica was evaluated by in vivo micronuclei assay. We evaluated the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in peripheral blood samples from pups and MNPCE and PCE in pregnant rats. No genotoxic effect was observed after oral administration of the three different doses of aqueous root total extract of J. dioica in pregnant or in their newborn pubs, after transplacental exposure. A significant decrease in PCE frequency was noted in samples from pubs of rats treated with the highest dose of J. dioica extract. The aqueous total root extract of J. dioica at the highest dose tested in our research do have cytotoxic effect in pups transplacentally exposed to this plant extract. Moreover, neither a genotoxic nor a cytotoxic effect was observed in pregnant rats. In the present work, there was no evidence of genome damage in the rat model after transplacental exposure to J. dioica aqueous root total extract.
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PURPOSE: The rs2234693 and rs9340799 ESR1 polymorphisms have shown contradictory results in studies of breast cancer (BC). The purpose of this study was to determine the frequency and association of ESR1 polymorphisms (rs2234693 and rs9340799) in BC patients of Mexican population. METHODS: PCR was used to genotype rs2234693 and rs9340799 polymorphisms in the ESR1 gene in Mexican healthy subjects and breast cancer (BC) patients. RESULTS: The frequency of cases and control groups of rs2234693 and rs9340799 polymorphisms in the ESR1 was similar, and none has shown any association with increased BC risk (p>0.05), although the association between the haplogenotypes (rs2234693 and rs9340799 polymorphisms) and BC patients with miscarriages [CTAG variant, adjusted odds ratio (OR) 1.83 (95%CI 1.17-2.86);p=0.011] and tobacco consumption [CCGG variant, adjusted OR 1.88 (95%CI 1.11-3.19);p=0.018] was evident. Also, the homozygous genotype TT [rs2234693, OR 1.49 (95%CI 1.02-2.19);p=0.042] and GG [rs9340799, OR 2.85 (95%CI 1.144-7.10);p=0.024] showed marginal association with BC, indicating that these factors may contribute significantly to the susceptibility of risk to BC. The TA haplotype was more common in controls than in CG. BC patients with a frequency around 0.71 among study groups, but without significant difference (p>0.05). CONCLUSION: rs2234693 and rs9340799 polymorphisms in the ESR1 gene were not associated with susceptibility for BC. However, the haplogenotypes CTAG and CCGG of rs2234693 and rs9340799 polymorphisms could contribute significantly to the susceptibility of risk in BC positive at miscarriage and tobacco consumption in this sample population.