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Article ; Online: Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents.

Jiménez-Garza, Octavio / Ghosh, Manosij / Barrow, Timothy M / Godderis, Lode

2023 Volume 11, Page(s) 1073658

Abstract: Introduction: Epigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells ... ...

Abstract	Introduction: Epigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells have been performed. The goal of this review is to summarize and contrast findings about DNA methylation in blood cells from workers exposed to toxicants. Methods: A literature search was performed using PubMed and Web of Science. After first screening, we discarded all studies performed Discussion: Some evidence from longitudinal studies suggest that modifications observed in cross-sectional designs may be transitory; then, we cannot say that DNA methylation changes are predictive of disease development due to those exposures. Conclusion: Due to the heterogeneity in the genes studied, and scarcity of longitudinal studies, we are far away from considering DNA methylation changes as biomarkers of effect in occupational exposures, and nor can we establish a clear functional or pathological correlate for those epigenetic modifications associated with the studied exposures.
MeSH term(s)	DNA Methylation ; Cross-Sectional Studies ; Epigenesis, Genetic ; Biomarkers ; Blood Cells
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-02-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1073658
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Acerca de complementar investigación cuantitativa con cualitativa en atención primaria: La narrativa de las personas no muestra valor de «p».

Jiménez-Garza, Octavio / Arroyo Rojas, Lellanis

Atencion primaria

2022 Volume 54, Issue 12, Page(s) 102500

Title translation	About complementing quantitative with qualitative research in primary care: Narrative of people does not show a «p» value.
Language	Spanish
Publishing date	2022-11-05
Publishing country	Spain
Document type	Letter
ZDB-ID	1200787-0
ISSN	1578-1275 ; 0212-6567
ISSN (online)	1578-1275
ISSN	0212-6567
DOI	10.1016/j.aprim.2022.102500
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Article: Inflammation and Oxidative Stress Induced by Obesity, Gestational Diabetes, and Preeclampsia in Pregnancy: Role of High-Density Lipoproteins as Vectors for Bioactive Compounds.

Jiménez-Osorio, Angélica Saraí / Carreón-Torres, Elizabeth / Correa-Solís, Emmanuel / Ángel-García, Julieta / Arias-Rico, José / Jiménez-Garza, Octavio / Morales-Castillejos, Lizbeth / Díaz-Zuleta, Hugo Alexander / Baltazar-Tellez, Rosa María / Sánchez-Padilla, María Luisa / Flores-Chávez, Olga Rocío / Estrada-Luna, Diego

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 10

Abstract: Inflammation and oxidative stress are essential components in a myriad of pathogenic entities that lead to metabolic and chronic diseases. Moreover, inflammation in its different phases is necessary for the initiation and maintenance of a healthy ... ...

Abstract	Inflammation and oxidative stress are essential components in a myriad of pathogenic entities that lead to metabolic and chronic diseases. Moreover, inflammation in its different phases is necessary for the initiation and maintenance of a healthy pregnancy. Therefore, an equilibrium between a necessary/pathologic level of inflammation and oxidative stress during pregnancy is needed to avoid disease development. High-density lipoproteins (HDL) are important for a healthy pregnancy and a good neonatal outcome. Their role in fetal development during challenging situations is vital for maintaining the equilibrium. However, in certain conditions, such as obesity, diabetes, and other cardiovascular diseases, it has been observed that HDL loses its protective properties, becoming dysfunctional. Bioactive compounds have been widely studied as mediators of inflammation and oxidative stress in different diseases, but their mechanisms of action are still unknown. Nonetheless, these agents, which are obtained from functional foods, increase the concentration of HDL, TRC, and antioxidant activity. Therefore, this review first summarizes several mechanisms of HDL participation in the equilibrium between inflammation and oxidative stress. Second, it gives an insight into how HDL may act as a vector for bioactive compounds. Third, it describes the relationships between the inflammation process in pregnancy and HDL activity. Consequently, different databases were used, including MEDLINE, PubMed, and Scopus, where scientific articles published in the English language up to 2023 were identified.
Language	English
Publishing date	2023-10-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12101894
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Article ; Online: Possible role of n-hexane as an endocrine disruptor in occupationally exposed women at reproductive age.

Ruiz-García, Liliana / Figueroa-Vega, Nicté / Malacara, Juan M / Barrón-Vivanco, Briscia / Salamon, Fabiola / Carrieri, Mariella / Jiménez-Garza, Octavio

Toxicology letters

2020 Volume 330, Page(s) 73–79

Abstract: Human exposure to n-hexane has been associated with subfertility and, experimentally, with a decrease in follicular development. In order to assess occupational exposure to n-hexane on ovarian function and gonadotropic hormones, we studied Mexican women ... ...

Abstract	Human exposure to n-hexane has been associated with subfertility and, experimentally, with a decrease in follicular development. In order to assess occupational exposure to n-hexane on ovarian function and gonadotropic hormones, we studied Mexican women labouring in a leather shoe factory (n = 34). Individual environmental levels for seven solvents, n-hexane included, were measured; also, urinary 2,5-hexanedione (2,5-HD) was determined. For ovarian function and hormonal status, FSH, LH, oestradiol and anti-Müllerian hormone (AMH) levels were determined. We performed all determinations also in a reference group, administrative workers with no exposure to solvents (n = 32). Results: N-hexane and urinary 2,5-HD levels were higher in exposed group (p < 0.001). More cases of oligomenorrhea as well as longer time for getting pregnant were observed in exposed women compared with controls; a positive association was found between menstrual cycle length and "time for getting pregnant" (p = 0.010); significant associations between FSH serum levels and 2,5-HD urinary levels (post-shift sample) were observed in non-smokers participants presenting oligomenorrhea from exposed group. Also, we found a trend for lower oestradiol levels in exposed participants with current smoking habit (p = 0.059). Conclusions: 2,5-HD urinary levels are associated with decreased gonadotropins levels; hence, n-hexane should be considered an endocrine disruptor in reproductive-age women.
Language	English
Publishing date	2020-05-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2020.04.022
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Article ; Online: 5'UTR methylation in different genes from workers exposed to volatile organic compounds: A new insight for considering an epigenetic mark as a functional correlate.

Jiménez-Garza, Octavio / Linares-Segovia, Benigno / Ruiz-García, Liliana / Monroy-Torres, Rebeca / Hernández-Luna, Marco Antonio

Toxicology letters

2020 Volume 330, Page(s) 59–64

Abstract: Gene-specific methylation has been related with transcriptional/translational consequences in different cells; also, this epigenetic modification is affected by environmental exposures. In previous studies, CYP2E1 activity in toluene-exposed workers was ... ...

Abstract	Gene-specific methylation has been related with transcriptional/translational consequences in different cells; also, this epigenetic modification is affected by environmental exposures. In previous studies, CYP2E1 activity in toluene-exposed workers was decreased compared to controls, however, CYP2E1 promoter methylation levels did not show significant differences. Here, we compared gene-specific methylation levels at the 5'UTR region, in a subset of workers whom already participated in two former studies, compared to controls. Methods: DNA was obtained from whole blood in five different groups: occupationally exposed to a mixture of volatile organic compounds (VOC): high levels (n = 19); low levels (n = 19) and very low levels (n = 17), toluene-exposed workers (n = 19) and control group (n = 19). We performed PCR-pyrosequencing at the 5'UTR region from four genes: CYP2E1, IL-6, SOD1 and TNF-α. Results: In participants exposed to high levels of a VOC mixture, we found significant differences: lower methylation levels for IL-6, and higher methylation levels for TNF-α compared to controls. In toluene-exposed workers, we found significant, lower methylation levels for CYP2E1 compared to controls. Conclusion: Lower methylation levels at the 5'UTR region from CYP2E1 in toluene exposed-workers, suggests that this epigenetic modification could represent a functional correlate regarding enzymatic activity, as a response to toluene biotransformation.
Language	English
Publishing date	2020-05-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2020.05.001
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Article ; Online: Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review.

Alvarado-Cruz, Isabel / Alegría-Torres, Jorge A / Montes-Castro, Nereida / Jiménez-Garza, Octavio / Quintanilla-Vega, Betzabet

Annals of global health

2018 Volume 84, Issue 2, Page(s) 212–224

Abstract: Background: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is ... ...

Abstract	Background: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors. Objective: This review focuses on DNA-methylation and its association with environmental-related diseases in children. Methods: A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected. Findings: Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases. Conclusions: Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.
MeSH term(s)	Child ; Child Health ; DNA Methylation/genetics ; Environmental Exposure/adverse effects ; Environmental Exposure/prevention & control ; Environmental Health/methods ; Environmental Health/organization & administration ; Epigenesis, Genetic ; Female ; Humans ; Maternal Exposure/adverse effects ; Maternal Exposure/prevention & control ; Risk Factors
Language	English
Publishing date	2018-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2821756-1
ISSN	2214-9996 ; 2214-9996
ISSN (online)	2214-9996
ISSN	2214-9996
DOI	10.29024/aogh.909
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Article ; Online: Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture.

Jiménez-Garza, Octavio / Guo, Liqiong / Byun, Hyang-Min / Carrieri, Mariella / Bartolucci, Giovanni Battista / Barrón-Vivanco, Briscia Socorro / Baccarelli, Andrea A

Toxicology and applied pharmacology

2018 Volume 339, Page(s) 65–72

Abstract: Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways ... ...

Abstract	Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways. Peripheral blood samples and individual-level VOC exposure data were obtained from healthy leather shoe factory workers (LS, n=40) and gas station attendants (GS, n=36), as well as a reference group of university employees (C, n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane, toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels were higher in GS (p<0.001). TOP2A, SOD1, and TNF-α promoter methylation status was increased in LS (p<0.05). In LS, we also found significant correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008) and COX-2 (r=-0.38, p=0.007) methylation. In exposed groups, ethylbenzene exposure levels showed a significant correlation with TOP2A methylation (β=0.33). Our results show early, toxic effects at the epigenetic level caused by occupational exposure to high levels of a VOC mixture. These subcellular modifications may represent the initial mechanism of toxicity leading to hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of VOC mixtures.
MeSH term(s)	Adolescent ; Adult ; Benzene Derivatives/toxicity ; DNA Methylation/drug effects ; DNA Methylation/physiology ; Female ; Hematologic Neoplasms/blood ; Hematologic Neoplasms/chemically induced ; Hematologic Neoplasms/genetics ; Humans ; Male ; Middle Aged ; Occupational Exposure/adverse effects ; Promoter Regions, Genetic/drug effects ; Promoter Regions, Genetic/physiology ; Volatile Organic Compounds/toxicity ; Young Adult
Chemical Substances	Benzene Derivatives ; Volatile Organic Compounds ; ethylbenzene (L5I45M5G0O)
Language	English
Publishing date	2018--15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2017.12.002
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Article ; Online: Promoter methylation status in genes related with inflammation, nitrosative stress and xenobiotic metabolism in low-level benzene exposure: Searching for biomarkers of oncogenesis.

Jiménez-Garza, Octavio / Guo, Liqiong / Byun, Hyang-Min / Carrieri, Mariella / Bartolucci, Giovanni Battista / Zhong, Jia / Baccarelli, Andrea A

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2017 Volume 109, Issue Pt 1, Page(s) 669–676

Abstract: Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we ... ...

Abstract	Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we studied promoter DNA methylation of IL6, CYP2E1 and iNOS in blood cells from three groups of workers: a) gas station attendants (GS) exposed to low levels of benzene; b) plastic shoe factory workers (PS) exposed to other solvents different to benzene and c) administrative workers as a reference group with no solvent exposure (C). Results: IL6 promoter methylation was higher in GS workers (p < 0.05). Also in GS, CYP2E1 promoter methylation negatively correlated with benzene levels (r = -0.47, p < 0.05); iNOS promoter methylation positively correlated with CYP2E1 promoter methylation (r = 0.29, p < 0.05), cumulative time of exposure (r = 0.31, p < 0.05) as well as with urinary levels of S- Phenyl mercapturic acid (SPMA), (r = 0.55, p < 0.05). Our results demonstrate alterations in the inflammation pathway at the epigenetic level associated with exposure to benzene. Correlations between iNOS methylation with both CYP2E1 methylation and urinary SPMA levels represent novel evidence about CYP2E1 epigenetic regulation and activity related with nitrosative stress, making promoter methylation status of these genes a potential biomarker in early stages of oncogenesis.
Language	English
Publishing date	2017-11
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2017.08.019
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Article ; Online: CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

Jiménez-Garza, Octavio / Baccarelli, Andrea A / Byun, Hyang-Min / Márquez-Gamiño, Sergio / Barrón-Vivanco, Briscia Socorro / Albores, Arnulfo

Toxicology and applied pharmacology

2015 Volume 286, Issue 3, Page(s) 207–215

Abstract: Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, ...

Abstract	Background: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. Goal: To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. Methods: We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. Results: In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively). Conclusion: These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression.
MeSH term(s)	Adult ; Cytochrome P-450 CYP2E1/physiology ; Epigenesis, Genetic/drug effects ; Epigenesis, Genetic/physiology ; Humans ; Male ; Middle Aged ; Occupational Exposure/adverse effects ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Smoking/adverse effects ; Smoking/blood ; Smoking/epidemiology ; Toluene/toxicity ; Young Adult
Chemical Substances	Toluene (3FPU23BG52) ; Cytochrome P-450 CYP2E1 (EC 1.14.13.-)
Language	English
Publishing date	2015-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2015.04.016
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Article ; Online: CYP2E1 phenotype in Mexican workers occupationally exposed to low levels of toluene.

Jiménez-Garza, Octavio / Márquez-Gamiño, Sergio / Albores, Arnulfo / Caudillo-Cisneros, Cipriana / Carrieri, Mariella / Bartolucci, Giovanni Battista / Manno, Maurizio

Toxicology letters

2012 Volume 210, Issue 2, Page(s) 254–263

Abstract: Unlabelled: CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment ...

Abstract	Unlabelled: CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test. Goal: To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México. Material and methods: (1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone. Results: Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p<0.001). Also, in this group CYP2E1 activity was lower (p<0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p<0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers. Conclusion: In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.
MeSH term(s)	Air Pollutants ; Air Pollution, Indoor ; Biomarkers ; Cytochrome P-450 CYP2E1/blood ; Cytochrome P-450 CYP2E1/genetics ; Cytochrome P-450 CYP2E1/metabolism ; Environmental Monitoring/methods ; Gene Expression Regulation, Enzymologic/physiology ; Hippurates/urine ; Humans ; Mexico ; Occupational Exposure/analysis ; Smoking ; Tanning ; Toluene/blood ; Toluene/chemistry ; Toluene/metabolism
Chemical Substances	Air Pollutants ; Biomarkers ; Hippurates ; Toluene (3FPU23BG52) ; Cytochrome P-450 CYP2E1 (EC 1.14.13.-) ; hippuric acid (TE0865N2ET)
Language	English
Publishing date	2012-04-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2012.01.021
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