Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers

Liu, Yuhang; Bai, Yansen; Wu, Xiulong; Li, Guyanan; Wei, Wei; Fu, Wenshan; Wang, Gege; Feng, Yue; Meng, Hua; Li, Hang; Li, Mengying; Guan, Xin; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Guo, Huan

doi:10.1016/j.envpol.2019.113655

Cited by 23 publications

(15 citation statements)

References 34 publications

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“…The emerging picture is that LOY is in part determined by genetic predisposition to deficiencies in DNA damage response-either through genetic effects that promote chromosome mis-segregation or failure in the molecular machinery to detect and appropriately deal with this damage. The remaining part might be due to other risk factors, e.g., smoking and environmental hazards [18][19][20].…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression

Dumanski

Halvardson

Davies

et al. 2021

Cell. Mol. Life Sci.

111

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Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.

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Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression

Dumanski

Halvardson

Davies

et al. 2021

Cell. Mol. Life Sci.

111

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show abstract

“…14 Other reported risk factors for LOY in blood include smoking, 7,8,10,14,24 obesity 14 and exposure to environmental risk factors such as air pollution 25 and polycyclic aromatic hydrocarbons. 26 For example, we showed that current smokers have an up to 4-fold increased risk of being affected compared with never smokers, with the increase being dose-dependent, and that smoking cessation is associated with recovery from LOY. 24 The transient effect from smoking has been replicated 7 and causality established by Mendelian randomization.…”

mentioning

confidence: 80%

Chromosome Y loss and drivers of clonal hematopoiesis in myelodysplastic syndrome

Baliakas

Forsberg

2021

haematol

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“…Another recent study that probed the combined effect of PAHs and phthalates exposure on telomere length and lung function in a pilot study conducted during the winter of 2014 and summer of 2015 in Wuhan city, China, revealed that 8 urinary monohydroxylated-PAHs (OH-PAHs) showed an overall effect on telomere length or lung function (Hou et al, 2020). When a study consisting of coke-oven workers (n = 1,005, males) looked at the association of PAH exposure and mosaic loss of chromosome Y (mLOY), one of the most common structure somatic event contributing to disease and mortality, found that a 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP) resulted in increased incidence of mLOY in a dosedependent linear association (Liu et al, 2020). In another study that monitored healthy women residing in the Cape Town region of South Africa revealed that levels of personal NO 2 and benzene exposure was inversely associated with leukocyte telomere length, where the magnitude of effects corresponded to > 6 year increase in chronological age (Everson et al, 2020).…”

Section: Nilson 2002mentioning

confidence: 99%

The Chemical Exposome of Human Aging

Misra

2020

Front. Genet.

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Aging is an inevitable biological phenomenon displayed by single cells and organs to entire organismal systems. Aging as a biological process is characterized as a progressive decline in intrinsic biological function. Understanding the causative mechanisms of aging has always captured the imagination of researchers since time immemorial. Although both biological and chronological aging are well defined and studied in terms of genetic, epigenetic, and lifestyle predispositions, the hallmarks of aging in terms of small molecules (i.e., endogenous metabolites to chemical exposures) are limited to obscure. On top of the endogenous metabolites leading to the onset and progression of healthy aging, human beings are constantly exposed to a natural and anthropogenic “chemical” environment round the clock, from conception till death, affecting one’s physiology, health and well-being, and disease predisposition. The research community has started gaining sizeable insights into deciphering the aging factors such as immunosenescence, nutrition, frailty, inflamm-aging, and diseases till date, without much input from their interaction with exogenous chemical exposures. The “exposome” around us, mostly, accelerates the process of aging by affecting the internal biological pathways and signaling mechanisms that result in the deterioration of human health. However, the entirety of exposome on human aging is far from established. This review intends to catalog the known and established associations of the exposome from past studies focusing on aging in humans and other model organisms. Further discussed are the current technologies and informatics tools that enable the study of aging exposotypes, and thus, provide a window of opportunities and challenges to study the “aging exposome” in granular details.

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Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers

Cited by 23 publications

References 34 publications

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression

Chromosome Y loss and drivers of clonal hematopoiesis in myelodysplastic syndrome

The Chemical Exposome of Human Aging

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