Cytogenotoxicity effects in addicts with multidrug consumption.

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.

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

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.

Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide.

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.

AURKA Gene Variants rs1047972, and rs8173 Are Associated With Breast Cancer.

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.

Evaluation of Genotoxic Effect and Antigenotoxic Potential against DNA Damage of the Aqueous and Ethanolic Leaf Extracts of Annona muricata Using an In Vivo Erythrocyte Rodent Micronucleus Assay.

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.

Micronuclei and Nuclear Buds Induced by Cyclophosphamide in Crocodylus moreletii as Useful Biomarkers in Aquatic Environments.

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.

Genomic instability in people living with HIV.

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.

Cytogenotoxicity Evaluation of Young Adults Exposed to High Levels of Air Pollution in a Mexican Metropolitan Zone Using Buccal Micronucleus Cytome Assay.

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).

Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice.

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.

Protective effect of rs712 polymorphism in a let-7 microRNA-binding of KRAS gene in breast cancer of a Mexican population.

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.

Genome Damage in Rats after Transplacental Exposure to Jatropha dioica Root Extract.

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.

Association of rs712 polymorphism in a let-7 microRNA-binding site of KRAS gene with colorectal cancer in a Mexican population.

OBJECTIVES: The rs712 polymorphism in a let-7 microRNA-binding site at KRAS gene has been associated with cancer. To examine its association with rs712 polymorphism, we analyzed Mexican individuals with colorectal cancer (CRC) and healthy subjects. MATERIALS AND METHODS: Genotyping of the rs712 polymorphism was performed by polymerase chain reaction in 281 controls and 336 CRC patients. RESULTS: The observed frequencies of rs712 polymorphism indicated an associated protective factor for CRC (P=0.032). An association between genotype and the disease was evident in: colon localization (allele T, odds ratio (OR) 3.82, 95% confidence Intervals (CI) 2.77-5.28, P=0.0001), node metastasis (genotype TT, OR 2.49, 95% CI 1.45-4.28, P=0.0009), poor differentiation (genotype GT, OR 2.35, 95% CI 1.35-4.1, P=0.0033), and poor chemotherapy response (genotype GT, OR 2.6, 95% CI 1.7-4.24, P=0.0001). CONCLUSION: Comparison of the data from patients with control group showed that polymorphism of rs712 in KRAS gene was protective factor, which was associated with susceptibility for CRC. However, the genotypes TT and GT of rs712 polymorphism in KRAS could contribute significantly to colon localization, node metastasis, poor differentiation and poor chemotherapy response in CRC patients in this sample population.

Macrophage Migration Inhibitory Factor Levels in Gingival Crevicular Fluid, Saliva, and Serum of Chronic Periodontitis Patients.

Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.

In vivo evaluation of the genotoxicity and oxidative damage in individuals exposed to 10% hydrogen peroxide whitening strips.

OBJECTIVE: This study assessed the impact of 10% hydrogen peroxide whitening strip exposure on the genotoxicity and oxidative damage by means of the buccal micronucleus cytome assay by counting nuclear abnormalities (NAs) in buccal mucosa and attached gingiva cells and by analyzing in whole saliva the molecule 8-hydroxy-2'-deoxyguanosine (8-OHdG). MATERIALS AND METHODS: The study was conducted on 113 subjects divided into two groups: group 1 or control (n = 53), non-whitening strip exposed, and group 2 (n = 60), whitening strip exposed (Crest® 3D Whitestrips® premium plus, 10% hydrogen peroxide). Oral epithelial cells and whole saliva samples were taken at the beginning and 30 days later for group 1 and immediately before bleaching and 15 and 30 days after the end of the bleaching for group 2. RESULTS: An increased frequency of NAs (p < 0.05) and higher levels of 8-OHdG (p < 0.05) were observed after bleaching exposure. Also, a positive correlation exists between oxidative stress produced by hydrogen peroxide and micronuclei was found. CONCLUSION: Individuals exposed to 10% hydrogen peroxide whitening strips exhibit NAs increased in oral epithelial cells and 8-OHdG in saliva, which is directed related to nuclear and oxidative DNA damage, respectively. CLINICAL SIGNIFICANCE: Hydrogen peroxide is the active agent of tooth whitening and this compound induced DNA damage. Individuals exposed to whitening strips with 10% hydrogen peroxide exhibit increased genotoxic and oxidative damage. Therefore, self-application of bleaching agents should be handled carefully since it could be a risk to human health.

Association of the IL-10 gene rs1800872 (-592 C>A) polymorphism with breast cancer in a Mexican population.

PURPOSE: Interleukin 10 (IL-10) gene polymorphisms are associated with different types of cancer, but these associations are inconsistent. The purpose of this study was to determine the frequency and association of the rs1800872 IL-10 gene polymorphism in Mexican women with breast cancer (BC). METHODS: The rs1800872 polymorphism was genotyped in 368 BC patients and 320 control women using the polymerase chain reaction (PCR). RESULTS: The rs1800872 polymorphism was a risk factor for BC compared to controls and BC patients with genotypes CA (p=0.004) and AA, and in the recessive model (p=0.0002), dominant model (CA+AA; p=0.0001), and allele A ( p=0.0001). Additionally, differences were observed in BC patients with the CA and CAAA genotypes who had chemotherapy gastric and hematological toxicity (p=0.022) and tumor stage IV (p=0.013) as a risk factor. Genotypes were CA in breastfeeding (p=0.017), AA in gastric toxicity (p=0.048), and CAAA in tumor stage I-II (p=0.019) as protective risk factors. In BC carriers of: 1) CAAA genotype with tumor stage I-II and breast feeding (≥6 months), 2) CA genotype BC Luminal A with tumor stage I-II, 3) CA genotype BC Luminal B with breastfeeding (≥6 months), and 4) CAAA genotypes in BC HER2 with indices of cellular proliferation (Ki-67) that were elevated (≥20%), were considered to be protective factors in BC patients. CONCLUSION: The IL-10 gene rs1800872 polymorphism was associated with BC susceptibility in this sample from the Mexican population.

TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients.

OBJECTIVE: To examine the association between TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation by comparing healthy subjects with colorectal cancer (CRC) patients in the Mexican population. METHOD: Genotyping of the 2R/3R was performed by polymerase chain reaction (PCR) and [IVS]14+1G>A mutation by real-time PCR analysis. RESULTS: The observed frequencies of the TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD did not indicate an increased risk for CRC (p>0.05). However we observed an association of the 2R/2R (OR 3.08, 95% CI 1.66-6.08, p=0.0017) and heterozygous (OR 1.98, 95% CI 1.32-2.97, p=0.0012) genotypes as risk factors when comparing controls and CRC patients that were also tobacco consumers. An association between the genotype and the disease was evident. The distribution of the 2R/2R genotype and hematological toxicity (adjusted OR 2.26, 95% CI 1.54-4.45, p=0.0259), heterozygous (2R/3R) with tumor stage III-IV (OR 1.81, 95% CI 1.11-2.94, p=0.020) and 2R/2R-2R/3R in non-chemotherapy response CRC patients with hematological (OR 2.3, 95% CI 1.21-4.4, p=0.014) and gastric toxicities (OR 3.11, 95% CI 1.18-8.2, p=0.035) confirmed that this factor may significantly contribute to the CRC susceptibility. CONCLUSION: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

Micronuclei and nuclear anomalies in Mexico's indigenous population.

OBJECTIVE: To determine the number of micronuclei and nuclear anomalies in Mexico's indigenous population. MATERIALS AND METHODS: One hundred twenty indigenous individuals were evaluated, including thirty from the ethnicities Cora, Huichol, Tarahumara and Tepehuano. The number of micronuclei (MN) and any nuclear abnormality (NA) in oral mucosa cells, including cells with nuclear buds, binucleated cells, cells with karyolysis, karyorrhetic, condensed chromatin and pyknotic cells were determined for each participant. RESULTS: Tepehuano and Tarahumaras showed the greatest damage to DNA. The Tepehuano group presented the highest number of MN and NA, this being a significant difference (p < 0.05) compared with the rest of the studied groups. This group also presented the highest herbicide exposure (46.7%). In relation to the smoking and drinking habits, these were more frequent in the Tarahumara group (33.3 and 50% respectively). CONCLUSION: The ethnic diversity, habits and customs may influence the DNA nuclear integrity in the Amerindian groups.

Micronuclei and nuclear anomalies in Mexico's indigenous population / Micronúcleos y anormalidades nucleares en población indígena de México

Abstract: Objective: To determine the number of micronuclei and nuclear anomalies in Mexico's indigenous population. Materials and methods: One hundred twenty indigenous individuals were evaluated, including thirty from the ethnicities Cora, Huichol, Tarahumara and Tepehuano. The number of micronuclei (MN) and any nuclear abnormality (NA) in oral mucosa cells, including cells with nuclear buds, binucleated cells, cells with karyolysis, karyorrhetic, condensed chromatin and pyknotic cells were determined for each participant. Results: Tepehuano and Tarahumaras showed the greatest damage to DNA. The Tepehuano group presented the highest number of MN and NA, this being a significant difference (p < 0.05) compared with the rest of the studied groups. This group also presented the highest herbicide exposure (46.7%). In relation to the smoking and drinking habits, these were more frequent in the Tarahumara group (33.3 and 50% respectively). Conclusion: The ethnic diversity, habits and customs may influence the DNA nuclear integrity in the Amerindian groups.

Resumen: Objetivo: Determinar el número de micronúcleos y anomalías nucleares en la población indígena de México. Material y métodos: Se evaluó a ciento veinte indígenas, incluyendo treinta individuos de las etnias cora, huichol, tarahumara y tepehuana. A cada participante se le determinó el número de micronúcleos (MN) y de alguna anomalía nuclear (AN) en células de mucosa bucal, incluyendo células con brotes nucleares, binucleadas, cariolisis, cariorrexis, cromatina condensada y picnóticas. Resultados: Los tepehuanos y tarahumaras mostraron el mayor daño al ADN. El grupo tepehuano presentó el mayor número de MN y AN, con una diferencia significativa (p < 0.05) en comparación con el resto de los grupos estudiados; este grupo presentó también la mayor exposición a herbicidas (46.7%). En relación con los hábitos de fumar y beber, se presentaron con mayor frecuencia en el grupo tarahumara (33.3 y 50%, respectivamente). Conclusión. La diversidad étnica, hábitos y costumbres pueden influir la integridad del ADN en los grupos amerindios.

Genotoxic and cytotoxic evaluation of Jatropha dioica Sessé ex Cerv. by the micronucleus test in mouse peripheral blood.

Jatropha dioica Sessé ex Cerv. is a medicinal plant credited with low cytotoxicity in vitro. Thus, the objective of this work was to evaluate the possible genotoxic and cytotoxic effect in vivo of the J. dioica aqueous extract by means of micronucleus assay in mouse peripheral blood. Four different J. dioica aqueous extract dose-units were evaluated (30, 60, 100, and 300 mg/kg). The extract was administered orally to male Balb-C-strain mice every 24 h during 5 days. Blood samples were taken at 0, 24, 48, 72, 96, and 120 h from the mouse's tail and were performed in duplicate extensions. The number of Polychromatic Erythrocytes (PCE), Polychromatic Micronucleus Erythrocytes (PCEMN), and Micronucleus Erythrocytes (MNE) was determined at the different sampling times in the different study groups. Our results showed that the group that received 60 mg/kg of cyclophosphamide (positive control) presented a significant decrease in the PCE (p = 0.044) proportion and a significant increase in MNE (p = 0.032, p = 0.0001). The groups that received the different J. dioica aqueous extract doses did not present either a PCE decrease or an increase in PCEMN and MNE. J. dioica exerts neither a genotoxic nor a cytotoxic effect on mouse peripheral blood at high doses.

Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population.

INTRODUCTION: The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland. MATERIAL AND METHODS: We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC). RESULTS: The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1-2.6, p = 0.009, for the T1/T2-T2/T2 genotypes. The association was also evident when the distributions of the T1/T2-T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03-3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27-3.067, p = 0.002). CONCLUSIONS: The T1/T2-T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population.