Microcystin-LR increases genotoxicity induced by aflatoxin B1 through oxidative stress and DNA base excision repair genes in human hepatic cell lines

Liu, Wenyi; Wang, Lingqiao; Zheng, Chuanfen; Liu, Lebin; Jia, Wei‐Hua; Li, Daibo; Tan, Yao; Zhao, Xiuli; He, Liang-Ying; Shu, Weiqun

doi:10.1016/j.envpol.2017.10.067

Cited by 47 publications

(23 citation statements)

References 52 publications

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“…While the conventional treatment technologies can eliminate intact toxic cyanobacterial cells effectively, these technologies have limited capability for removal of dissolved cyanobacterial toxins, which allows that these reach human populations via drinking water supplies in sufficiently high concentrations to cause adverse effects in the gastrointestinal system (Table 1). Chronic exposures to drinking water contaminated with cyanobacterial compounds, in some instances in combination with other confounding factors, have been associated with an increased incidence of liver cancers or chronic liver damage and diseases, as reviewed and discussed by Svirčev et al [12], and supported by recent findings [18][19][20]. Interestingly, epidemiologic studies have also linked chronic exposures to drinking water contaminated with cyanobacteria and their metabolites to the increased incidence of colorectal or small intestinal cancer in China [21], Portugal [22], and Serbia [12,23], or stomach cancer mortality in China [24].…”

mentioning

confidence: 87%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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Background: Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro-, and neurotoxicity, than for effects on the gastrointestinal tract and the associated lymphoid tissue. Main body: The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human health-relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects, or both. Furthermore, cyanobacterial bloom lipopolysaccharides, other less studied metabolites and their mixtures have been also implicated to have a role in gastrointestinal inflammation. Conclusion: The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. In addition, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites such as aeruginosins, have to be toxicologically evaluated at distinct levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, which can be expected in drinking water supplies.

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mentioning

confidence: 87%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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“…While conventional treatment technologies can eliminate intact cyanobacterial cells with toxins quite effectively, these technologies have limited capability for removal of dissolved cyanobacterial toxins, which allows them to reach taps in sufficiently high concentrations to cause adverse effects in the gastrointestinal system (Table 1). Chronic exposures to drinking water contaminated with cyanobacterial compounds, in some instances in combination with other confounding factors, have been associated with an increased incidence of liver cancers or chronic liver damage and diseases, as reviewed and discussed by Svircev et al [12], and supported by recent findings [17][18][19]. Interestingly, epidemiologic studies have linked chronic exposures to drinking water contaminated with cyanobacteria and their metabolites also to the increased incidence of colorectal or small intestinal cancer in China, Portugal and Serbia, or stomach cancer mortality in China [12,20,21].…”

Section: Introductionmentioning

confidence: 84%

Effects of Cyanobacterial Toxins on the Human Gastrointestinal Tract and the Mucosal Innate Immune System

Kubíčková

Babica

Hilscherová

et al. 2019

Preprint

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Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro- and neurotoxicity, then for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies. studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies.

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“…DNA damage is enhanced when cells are exposed to both AFB1 and MC-LR, compared to the exposure to AFB1 or MC-LR, alone, because exposure to both AFB1 and MC-LR further increases the release of ROS. In this case, AFB1 induces genotoxicity through increasing oxidative stress and inhibiting the activity of DNA base excision repair genes [41]. Thus, induction of oxidative DNA damage is responsible for AFB1-induced hepatocarcinogenesis besides the elevated number of AFB1-DNA adducts.…”

Section: Afb1-induced Oxidative Stressmentioning

confidence: 99%

The Carcinogenicity of Aflatoxin B1

Li¹,

Liu²

2020

Aflatoxin B1 Occurrence, Detection and Toxicological Effects

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Aflatoxins are a class of carcinogenic mycotoxins, products of Aspergillus fungi, which are known contaminants in a large portion of the world's food supply. Aflatoxin B1 (AFB1) is the most potent toxin, which has been strongly linked to the development of hepatocellular carcinoma (HCC), especially given coinfection with hepatitis B virus (HBV). AFB1 is catalyzed by cytochrome P450 (CYP450) into aflatoxin B1-8,9-exo-epoxide to form DNA adducts, which leads to carcinogenesis by disrupting DNA repair. AFB1-induced DNA damage is also caused by the production of excessive ROS, leading to the oxidation of DNA bases. The majority of AFB1related to HCC carry G-toT transversion of p53 gene. When the p53 gene is mutated, it shows a "gain of oncogenic function." In addition, epigenetic alterations may potentially be beneficial for the treatment of HCC, because the epigenetic changes are reversible. This chapter will provide important information on the carcinogenicity of AFB1, including DNA damage checkpoint response and epigenetic alteration.

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Microcystin-LR increases genotoxicity induced by aflatoxin B1 through oxidative stress and DNA base excision repair genes in human hepatic cell lines

Cited by 47 publications

References 52 publications

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Effects of Cyanobacterial Toxins on the Human Gastrointestinal Tract and the Mucosal Innate Immune System

The Carcinogenicity of Aflatoxin B1

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