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.

mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

Mitochondrial Control Region Variants Related to Breast Cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Our purpose was to explore differences in mitochondrial sequences of cases with breast cancer compared with control samples from different origins. We identified 124 mtDNA sequences associated with breast cancer cases, of which 86 were complete and 38 were partial sequences. Of these 86 complete sequences, 52 belonged to patients with a confirmed diagnosis of breast cancer, and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From the mtDNA analysis, two polymorphisms with significant statistical differences were found: m.310del (rs869289246) in 34.6% (27/78) of breast cancer cases and 61.7% (21/34) in the controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) in the controls. In addition, the variant m.16519T>C (rs3937033) was found in 59% of the control sequences and 52% of the breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to the haplogroup H of Indo-European and Euro-Asiatic origins; however, they were found in all non-European breast cancers.

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.

[Type 2 diabetes nephropathy: a thresholds complex trait and chromosomal morbid map]. / Nefropatía por diabetes mellitus tipo 2: un rasgo multifactorial con umbral y su mapa mórbido cromosómico.

Type 2 diabetes nephropathy is a multifactorial trait whose threshold or limit for the phenotypic expression depends on the additive effect of multiple loci and environmental factors that are specific to each population. After the sequencing of human genome more susceptibility loci through linkage studies and association have been found. The association studies showed involvement 69 loci, whereas genetic linkage studies involved 24 loci. Among environmental factors, genetically unknown foods and excessive consumption of beverages with sweeteners has been reported. However, despite wide evidence in the genetic component in the development of kidney damage, the environment participation is not evident in several perinatal studies. One of the approaches proposed given the genetic heterogeneity that influences nephropathy, are epistasis studies, which will become increasingly important in the upcoming years.

[Lung cancer histological types and diagnostic methods in a tertiary care facility]. / Tipos histológicos y métodos diagnósticos en cáncer pulmonar en un centro hospitalario de tercer nivel.

OBJECTIVE: To describe the histological frequencies, diagnostic methods, gender and age of lung cancer patients in a third level care hospital in western Mexico. METHODS: A retrospective and descriptive study (2002 to 2005) was undertaken. From all reviewed cases, 242 patients had a diagnosis compatible with lung cancer. We analyzed the histological type, gender, age group, and diagnostic method. RESULTS: The histological type frequencies of lung cancer were as follows: 63.6% adenocarcinoma, 19.0% squamous cell carcinoma, 15.2% small cell carcinoma, and 2.2% large-cell carcinoma. Among these patients, a male-female ratio of 2:1 with a mean age of 63 years was found. Regarding the diagnostic methods followed, the most common included: transthoracic needle aspiration, bronchial biopsy, and bronchial washing. CONCLUSIONS: Adenocarcinoma was the most frequent histological type in the sample studied, an association between female gender and risk of developing adenocarcinoma was detected.

Tipos histológicos y métodos diagnósticos en cáncer pulmonar en un centro hospitalario de tercer nivel / Lung cancer histological types and diagnostic methods in a tertiary care facility

Objetivo: Describir las frecuencias de tipos histológicos, métodos diagnósticos, sexo y edad de pacientes con cáncer pulmonar, en el Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Jalisco. Métodos: Estudio descriptivo y retrospectivo de los casos revisados entre 2002 y 2005; 242 pacientes presentaron diagnóstico de cáncer pulmonar. Se analizó el tipo histológico, sexo, edad y métodos diagnósticos. Resultados: Los tipos histológicos de cáncer pulmonar presentaron las siguientes frecuencias: adenocarcinoma 63.6%, carcinoma de células escamosas 19.0%, carcinoma de células pequeñas 15.2% y carcinoma de células grandes 2.2%. Se encontró una relación varón:mujer de 2:1, con una edad promedio de 63 años. Los métodos diagnósticos más utilizados fueron biopsia por aspiración con aguja fina, biopsia bronquial y lavado bronquial. Conclusiones: En la población analizada, el adenocarcinoma fue el tipo histológico más frecuente. Además, se encontró asociación entre el sexo femenino y el riesgo de presentar adenocarcinoma.

OBJECTIVE: To describe the histological frequencies, diagnostic methods, gender and age of lung cancer patients in a third level care hospital in western Mexico. METHODS: A retrospective and descriptive study (2002 to 2005) was undertaken. From all reviewed cases, 242 patients had a diagnosis compatible with lung cancer. We analyzed the histological type, gender, age group, and diagnostic method. RESULTS: The histological type frequencies of lung cancer were as follows: 63.6% adenocarcinoma, 19.0% squamous cell carcinoma, 15.2% small cell carcinoma, and 2.2% large-cell carcinoma. Among these patients, a male-female ratio of 2:1 with a mean age of 63 years was found. Regarding the diagnostic methods followed, the most common included: transthoracic needle aspiration, bronchial biopsy, and bronchial washing. CONCLUSIONS: Adenocarcinoma was the most frequent histological type in the sample studied, an association between female gender and risk of developing adenocarcinoma was detected.