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.

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.

Association of genetic polymorphisms with histological grading of necroinflammation, staging of fibrosis, and liver function in Mexicans with chronic hepatitis C virus infection.

BACKGROUND/AIM: The aim of this work was to establish an association between the single-nucleotide polymorphisms (SNPs) of TGFB1 (rs1800471), AT (rs3789679), MMP-1 (rs17886084), MMP-3 (rs35068180), and PAI-1 (rs1799889) and the histological grading of necroinflammation, staging of hepatic fibrosis, and liver function in Mexican patients with advanced liver fibrosis due to chronic hepatitis C virus infection. METHODS: AT, MMP-1, MMP-3, and PAI-1 gene polymorphisms were analyzed by polymerase chain reaction in real time, whereas TGFB1 polymorphism was detected by polymerase chain reaction-based restriction fragment length polymorphism in 38 patients with established advanced liver fibrosis and 50 subjects from the general population. Grading of necroinflammation and staging of liver fibrosis were assessed by liver biopsy and graded according to modified histological activity index Ishak score. RESULTS: Regarding TGFB1 SNP, significant differences were found between G/G and G/C genotypes of patients with hepatic necroinflammation (P = 0.05) and hepatic fibrosis (P = 0.002). There were also significant differences among genotypes of patients with the AT SNP in hepatic necroinflammation (P = 0.01). The albumin-globulin ratio between genotypes of patients with the MMP-3 SNP gene showed significant differences (P = 0.02). CONCLUSION: Our findings demonstrate that a specific combination of genotypes associated with biochemical values and a histological high score determine more severe liver disease. The presence of the G/G genotype of TGFB1 SNP in patients was significantly associated with severity of liver necroinflammation and fibrosis. Patients with the G/G genotype of AT SNP were associated with severe necroinflammation. The albumin-globulin ratio was increased in patients with the 6A allele of MMP-3 SNP. These results might contribute to diagnosis and further establishment of liver disease treatment.

Controlled clinical trial with pirfenidone in the treatment of breast capsular contracture: association of TGF-ß polymorphisms.

BACKGROUND: Breast capsular contracture (BCC) is a commonly adverse event postmammoplastly characterized by an immune response mediated by cytokines and transforming growth factor (TGF)-ß1 resulting in excessive synthesis and deposit of extracellular matrix around the breast implant. Presence of TGF-ß1 polymorphisms has been associated as a risk factor to develop fibroproliferative diseases. METHODS: This open, controlled, prospective, and pilot clinical trial with 6 months duration was carried out to evaluate the efficacy of 1800 mg a day, of oral Pirfenidone (PFD) in the treatment of BCC (Baker Score III/IV) postmammoplasty. Twenty BCC cases received PFD and 14 BCC control cases underwent capsulectomy after 6 months of enrollment. Both groups were followed up for 6 more months up to 12 months to determine the relapse in the absence of PFD. Determination of TGF-ß1 polymorphisms was performed to establish a correlation with capsular contracture. RESULTS: PFD group experienced BCC-reduction in all breasts 6 months after enrollment. Only 1 of 20 cases relapsed after follow-up. In capsulectomy group, 2 of 14 cases presented progression to grade IV during presurgical period. All capsulectomy cases relapsed at end of follow-up. Nearly hundred percent of all patients studied in this protocol had a profibrogenic homozygous TGF-ß1 polymorphism (codon 25; genotype Arg25Arg). CONCLUSIONS: PFD is useful to improve BCC (Baker Score III/IV) postmammoplasty with no relapse after drug administration. There is also an association between capsular contracture and the presence of homozygous G/G TGF-ß1 genotype.