scholarly journals Carcinogens and DNA damage

2018 ◽  
Vol 46 (5) ◽  
pp. 1213-1224 ◽  
Author(s):  
Jessica L. Barnes ◽  
Maria Zubair ◽  
Kaarthik John ◽  
Miriam C. Poirier ◽  
Francis L. Martin
Keyword(s):  
Dna Damage ◽  
Cancer Risk ◽  
Epidemiological Studies ◽  
Heterocyclic Aromatic Amines ◽  
Migrant Populations ◽  
Wide Range ◽  
High Cancer Risk ◽  
Polycyclic Aromatic ◽  
Exogenous Agents ◽  
Cross Links

Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA–DNA or DNA–protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.

scholarly journals Epigenetic Influences in the Aetiology of Cancers Arising from Breast and Prostate: A Hypothesised Transgenerational Evolution in Chromatin Accessibility

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Francis L. Martin
Keyword(s):  
Target Genes ◽  
Epigenetic Modification ◽  
Intervention Strategy ◽  
Epidemiological Studies ◽  
Chromatin Accessibility ◽  
Dietary Factors ◽  
Heterocyclic Aromatic Amines ◽  
Tumour Suppressor Genes ◽  
Multistage Model ◽  
Migrant Populations

Epidemiological studies have consistently supported the notion that environmental and/or dietary factors play a central role in the aetiology of cancers of the breast and prostate. However, for more than five decades investigators have failed to identify a single cause-and-effect factor, which could be implicated; identification of a causative entity would allow the implementation of an intervention strategy in at-risk populations. This suggests a more complex pathoaetiology for these cancer sites, compared to others. When one examines the increases or decreases in incidence of specific cancers amongst migrant populations, it is notable that disease arising in colon or stomach requires one or at most two generations to exhibit a change in incidence to match that of high-incidence regions, whereas for breast or prostate cancer, at least three generations are required. This generational threshold could suggest a requirement for nonmutation-driven epigenetic alterations in the F0/F1 generations (parental/offspring adopting a more westernized lifestyle), which then predisposes the inherited genome of subsequent generations to mutagenic/genotoxic alterations leading to the development of sporadic cancer in these target sites. As such, individual susceptibility to carcinogen insult would not be based per se on polymorphisms in activating/detoxifying/repair enzymes, but on elevated accessibility of crucial target genes (e.g., oncogenes, tumour suppressor genes) or hotspots therein to mutation events. This could be termed a genomic susceptibility organizational structure (SOS). Several exposures including alcohol and heavy metals are epigens (i.e., modifiers of the epigenome), whereas others are mutagenic/genotoxic, for example, heterocyclic aromatic amines; humans are continuously and variously exposed to mixtures of these agents. Within such a transgenerational multistage model of cancer development, determining the interaction between epigenetic modification to generate a genomic SOS and genotoxic insult will facilitate a new level of understanding in the aetiology of cancer.

scholarly journals Dietary heterocyclic aromatic amine intake and cancer risk: epidemiological evidence from Japanese studies

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Motoki Iwasaki ◽  
Shoichiro Tsugane
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Colorectal Adenoma ◽  
Dietary Habits ◽  
Daily Intake ◽  
Epidemiological Studies ◽  
Heterocyclic Aromatic Amines ◽  
Cooking Methods ◽  
Case Control Studies ◽  
Significant Positive Association

AbstractHeterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated.

Adipose tissue, obesity and adipokines: role in cancer promotion

2015 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrea Booth ◽  
Aaron Magnuson ◽  
Josephine Fouts ◽  
Michelle Foster
Keyword(s):  
Adipose Tissue ◽  
Cancer Risk ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epidemiological Studies ◽  
Normal Weight ◽  
Cell Progression ◽  
High Cancer Risk ◽  
Apoptosis Pathways ◽  
And Migration

AbstractAdipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term “adiposopathy” is used to describe this promotion of pathogenic adipocytes and associated adipose – elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

scholarly journals Nation wide increase of polycyclic aromatic hydrocarbons in ultrafine particles during winter over China

2020 ◽  
Author(s):  
Qingqing Yu ◽  
Xiang Ding ◽  
Quanfu He ◽  
Weiqiang Yang ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Cancer Risk ◽  
Aromatic Hydrocarbons ◽  
Ultrafine Particles ◽  
Southern China ◽  
Northern China ◽  
Continental Scale ◽  
High Cancer Risk ◽  
Polycyclic Aromatic ◽  
One Year

Abstract. Polycyclic aromatic hydrocarbons (PAHs) are toxic compounds in the atmosphere and have adverse effects on public health, especially through the inhalation of particulate matter (PM). At present, there are limited understandings in size distribution of particulate-bound PAHs and its health risk on a continental scale. In this study, we carried out a one-year PM campaign and simultaneously measured size-segregated PAHs at 12 sites across six regions of China. The annual averages of total 24 PAHs (∑24PAHs) and benzo[a]pyrene (BaP) carcinogenic equivalent concentration (BaPeq) ranged from 7.56 to 205 ng m−3 with a mean of 53.5 ng m−3 and 0.21 to 22.2 ng m−3 with a mean of 5.02 ng m−3, respectively. At all the sites, ∑24PAHs and BaPeq were dominated in the ultrafine particles with aerodynamic diameter <1.1 μm, followed by those in the size ranges of 1.1–3.3 µm and >3.3 µm. Compared with the southern China, the northern China witnessed much higher ∑24PAHs (87.36 ng m−3 vs. 17.56 ng m−3), BaPeq (8.48 ng m−3 vs. 1.34 ng m−3) and PAHs inhalation cancer risk (7.4 × 10−4 vs. 1.2 × 10−4). Nationwide increases in both PAH levels and inhalation cancer risk occurred in winter. The unfavorable meteorological conditions and enhanced emissions of coal combustion and biomass burning together led to severe PAHs pollution and high cancer risk in the atmosphere of the northern China, especially during winter. Our results suggested that the reduction of coal and biofuel consumption in the residential sector could be crucial and effective to lower PAH concentrations and its inhalation cancer risk in China.

scholarly journals Intake of heterocyclic aromatic amines from meat in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort

2007 ◽  
Vol 98 (6) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sabine Rohrmann ◽  
Dorothee Zoller ◽  
Silke Hermann ◽  
Jakob Linseisen
Keyword(s):  
Cancer Risk ◽  
Aromatic Amines ◽  
Meat Consumption ◽  
Detailed Examination ◽  
Epidemiological Studies ◽  
Heterocyclic Aromatic Amines ◽  
Cooking Methods ◽  
Food Items ◽  
Meat Cooking ◽  
Prospective Investigation

It was the aim of the present study to estimate the intake of heterocyclic aromatic amines (HCA) from meat, which have been associated with cancer risk in several epidemiological studies, of 21 462 subjects who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg. This was accomplished by using a detailed dietary questionnaire that assessed meat consumption, cooking methods, and degree of browning of the respective food items. Median total HCA intake from meat was 31 ng/d (mean 69 ng/d), which was lower than results observed in previous studies. 2-Amino-1-methyl-6-phenylimidazo[4,5b]pyridine was the most common HCA in this cohort (median 17; mean 48 ng/d). The present study offers the opportunity of a detailed examination of the associations between meat cooking as well as HCA intake from meat and cancer risk in a prospective way.

scholarly journals Chromium exposure disrupts chromatin architecture upsetting the mechanisms that regulate transcription

2019 ◽  
Vol 244 (9) ◽  
pp. 752-757
Author(s):  
Hesbon A Zablon ◽  
Andrew VonHandorf ◽  
Alvaro Puga
Keyword(s):  
Dna Damage ◽  
Transcriptional Regulation ◽  
Cancer Risk ◽  
Hexavalent Chromium ◽  
Current Evidence ◽  
Area Of Interest ◽  
Wide Range ◽  
Contaminated Drinking Water ◽  
Epigenetic Signatures ◽  
The Impact

Hexavalent chromium (Cr(VI)) is a highly mutagenic and carcinogenic chemical used in many industrial processes. Occupational exposure to chromium, occurring mostly by inhalation, constitutes a major lung cancer risk affecting chromium workers. Environmental exposure, on the other hand, mainly by ingestion of contaminated drinking water, is a widespread gastrointestinal cancer risk, affecting millions of people throughout the world. One of the major mechanisms through which Cr(VI) causes carcinogenic transformation is thought to be the disruption of transcriptional regulation. Indeed, Cr(VI)-directed DNA damage and crosslinking occurs preferentially at sites where active DNA replication and transcription processes take place. Accordingly, numerous studies have shown that Cr(VI) causes gene expression changes in a wide range of cell signaling pathways, resulting from Cr(VI)-induced direct macromolecular damage, alteration in transcription factor function, and disruption of epigenetic signatures. This brief review highlights past and current information on the impact of Cr(VI) on the various mechanisms of transcriptional regulation. Impact statement This mini-review highlights current evidence on the mechanisms through which hexavalent chromium (Cr(VI)) disrupts transcriptional regulation, an emerging area of interest and one of the central processes by which chromium induces carcinogenesis. Several studies have shown that Cr(VI) causes widespread DNA damage and disrupts epigenetic signatures, suggesting that chromatin may be a direct Cr(VI) target. The findings discussed here suggest that Cr(VI) disrupts transcriptional regulation by causing genomic architecture changes.

scholarly journals The role of heterocyclic aromatic amines in colorectal cancer: the evidence from epidemiologic studies

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Loïc Le Marchand
Keyword(s):  
Colorectal Cancer ◽  
Aromatic Amines ◽  
Quantitative Methods ◽  
Biological Effects ◽  
Epidemiological Studies ◽  
Epidemiologic Studies ◽  
Red Meat ◽  
Heterocyclic Aromatic Amines ◽  
Intermediate Phenotype ◽  
Cancer Multiple

AbstractSince Dr. Sugimura’s discovery of heterocyclic aromatic amines (HAA) in broiled fish, many epidemiological studies have been conducted to investigate their role in human cancers, often focusing on colorectal cancer. The difficulty in measuring HAA exposure from meat and fish intake in these studies has resulted in inconsistent findings. Because studying individuals who may be particularly susceptible to the carcinogenic effects of HAA might facilitate the demonstration of a link with cancer, multiple studies have focused on individuals with the high activity phenotype for CYP1A2 and/or NAT2, the two main metabolic enzymes involved in the bioactivation of HAA. These investigations have also yielded inconsistent results. Two recent large pooled analyses of colorectal cancer studies have helped clarify the overall evidence. One was conducted in whites and reported no interaction of red meat intake and NAT2 genotype on risk in Whites. The other was conducted in Japanese and African Americans, two populations with high rates of the disease and a prevalence of the at-risk rapid NAT2 phenotype 10- and 2-fold greater than in whites, respectively. In those groups, a significant interaction was found, with the association of red meat with colorectal cancer being strongest among individuals with the rapid NAT2 phenotype, intermediate among those with the intermediate phenotype and not significant among those with the slow NAT2 phenotype. Recent research on biomarkers has focused on PhIP hair content, as a marker of exposure to HAA, and on DNA adducts using new sensitive quantitative methods, as markers of early biological effects. These advances, when brought to bear, may contribute greatly to the further elucidation of the carcinogenicity of HAA in humans.

scholarly journals Exposure to Particulate PAHs on Potential Genotoxicity and Cancer Risk among School Children Living Near the Petrochemical Industry

2021 ◽  
Vol 18 (5) ◽  
pp. 2575
Author(s):  
Nor Ashikin Sopian ◽  
Juliana Jalaludin ◽  
Suhaili Abu Bakar ◽  
Titi Rahmawati Hamedon ◽  
Mohd Talib Latif
Keyword(s):  
Cancer Risk ◽  
Environmental Protection Agency ◽  
Primary Schools ◽  
Petrochemical Industry ◽  
Industrial Area ◽  
Industrial Emissions ◽  
Buccal Cells ◽  
Genotoxic Effects ◽  
Lifetime Cancer Risk ◽  
Polycyclic Aromatic

This study aimed to assess the association of exposure to particle-bound (PM2.5) polycyclic aromatic hydrocarbons (PAHs) with potential genotoxicity and cancer risk among children living near the petrochemical industry and comparative populations in Malaysia. PM2.5 samples were collected using a low-volume sampler for 24 h at three primary schools located within 5 km of the industrial area and three comparative schools more than 20 km away from any industrial activity. A gas chromatography–mass spectrometer was used to determine the analysis of 16 United States Environmental Protection Agency (USEPA) priority PAHs. A total of 205 children were randomly selected to assess the DNA damage in buccal cells, employing the comet assay. Total PAHs measured in exposed and comparative schools varied, respectively, from 61.60 to 64.64 ng m−3 and from 5.93 to 35.06 ng m−3. The PAH emission in exposed schools was contributed mainly by traffic and industrial emissions, dependent on the source apportionment. The 95th percentiles of the incremental lifetime cancer risk estimated using Monte Carlo simulation revealed that the inhalation risk for the exposed children and comparative populations was 2.22 × 10−6 and 2.95 × 10−7, respectively. The degree of DNA injury was substantially more severe among the exposed children relative to the comparative community. This study reveals that higher exposure to PAHs increases the risk of genotoxic effects and cancer among children.

scholarly journals Exposure to Atmospheric Particulate Matter-Bound Polycyclic Aromatic Hydrocarbons and Their Health Effects: A Review

2021 ◽  
Vol 18 (4) ◽  
pp. 2177
Author(s):  
Lu Yang ◽  
Hao Zhang ◽  
Xuan Zhang ◽  
Wanli Xing ◽  
Yan Wang ◽  
...  
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Particulate Matter ◽  
Real Time ◽  
Health Effects ◽  
Aromatic Hydrocarbons ◽  
Anthropogenic Activities ◽  
Personal Exposure ◽  
Epidemiological Studies ◽  
Atmospheric Particulate Matter ◽  
Polycyclic Aromatic

Particulate matter (PM) is a major factor contributing to air quality deterioration that enters the atmosphere as a consequence of various natural and anthropogenic activities. In PM, polycyclic aromatic hydrocarbons (PAHs) represent a class of organic chemicals with at least two aromatic rings that are mainly directly emitted via the incomplete combustion of various organic materials. Numerous toxicological and epidemiological studies have proven adverse links between exposure to particulate matter-bound (PM-bound) PAHs and human health due to their carcinogenicity and mutagenicity. Among human exposure routes, inhalation is the main pathway regarding PM-bound PAHs in the atmosphere. Moreover, the concentrations of PM-bound PAHs differ among people, microenvironments and areas. Hence, understanding the behaviour of PM-bound PAHs in the atmosphere is crucial. However, because current techniques hardly monitor PAHs in real-time, timely feedback on PAHs including the characteristics of their concentration and composition, is not obtained via real-time analysis methods. Therefore, in this review, we summarize personal exposure, and indoor and outdoor PM-bound PAH concentrations for different participants, spaces, and cities worldwide in recent years. The main aims are to clarify the characteristics of PM-bound PAHs under different exposure conditions, in addition to the health effects and assessment methods of PAHs.

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