Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

Marchese, Silvia; Polo, Andrea; Ariano, Andrea; Velotto, Salvatore; Costantini, Susan; Severino, Lorella

doi:10.3390/toxins10060214

Cited by 360 publications

(219 citation statements)

References 103 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…Despite, none of the pasteurized milk samples exceeded the AFM 1 limit, and the mean levels of the samples were found to be 12.86 ng/L in the present study. Prolonged exposure to aflatoxin in small quantities can cause cancer and immunosuppression [32]. Thermal processes, such as pasteurization and sterilization, do not affect AFM 1 [6].…”

Section: Discussionmentioning

confidence: 99%

Determination of Aflatoxin M1 and Ochratoxin A in Raw, Pasteurized and UHT Milk in Turkey

Turkoglu

Keyvan

2019

Acta Scientiae. Vet.

View full text Add to dashboard Cite

Background:Mycotoxins produced by yeast and fungi have toxic effects on human and animal health. Aflatoxin B 1 (AFB 1 ) is the most toxic hepatocarcinogen to mammals. Aflatoxin M 1 (AFM 1 ), which has been found in milk and dairy products, is the hydroxylated metabolite of AFB 1 . Aflatoxin M 1 is formed by the cytochrome P450 enzyme in the liver. Ochratoxin A (OTA) is synthesized by Aspergillus and Penicillium species. Ochratoxin A is known to cause teratogenic, immunotoxic, nephrotoxic and carcinogenic effects. Due to the potential harmful effects on human and animal health, OTA has also been receiving increased attention globally; however, there is limited information on the presence of OTA in milk and dairy products. The aim of this study was to determine how mycotoxins impact the hygienic quality of raw and heat-processed milk. Materials, Methods & Results:In this study, a total of 105 milk samples were analyzed (35 raw, 35 pasteurized and 35 UHT) to identify AFM 1 and OTA in raw, pasteurized and ultra-high temperature processing (UHT) milk. The levels of AFM 1 were detected by using the enzyme-linked immunosorbent assay (ELISA). The milk samples were centrifuged in order to remove the fat content from the milk. After centrifugation, the upper cream layer was withdrawn with a pipette. The non-fat liquid portion was placed in wells at 100 μL for analysis. The concentration of AFM 1 in the milk samples was analyzed by AFM 1 test kit. The milk samples with AFM 1 levels greater than 50 ng/L were confirmed by using High-Performance Liquid Chromatography (HPLC). An Ochratoxin A Serum / Milk ELISA test kit was used for the analyses of OTA. The analyses were made according to the manufacturer's instructions, and samples were analyzed in duplicate. The absorbance value of milk samples was obtained from the ELISA plate reader at 450 nm. The mean value of AFM 1 was found to be 19.54 ng/L in the milk samples. According to the European Commission (EC), the maximum limit for AFM 1 in milk is 50 ng/L. In our study, eight (7.61%) of the 105 samples exceeded this limit. The mean value of OTA was found to be 119 ng/L in the milk samples. The relationship between milk type and levels of AFM 1 was found to be significant at (P < 0.01). The mean value of AFM 1 in pasteurized milk was found statistically significant and lower than raw milk (P < 0.05). The difference between levels of OTA and milk type was not statistically significant at (P > 0.05). Discussion: Milk is a great protein source especially for children in the age of growth. Yeasts such as Fusarium, Aspergillus and Penicillium produce mycotoxins that cause food, feed contamination. Owing to carcinogenic, mutagenic and teratogenic effects of AFM 1 , presence of AFM 1 in milk samples may adversely affect human health. The presence of AFM 1 in different contamination levels can be observed in milk and milk products. Factors such as ration type, climate conditions, feed storage conditions, feeding regime and health status of dairy animals may be effective in the occurrenc...

show abstract

Section: Discussionmentioning

confidence: 99%

Determination of Aflatoxin M1 and Ochratoxin A in Raw, Pasteurized and UHT Milk in Turkey

Turkoglu

Keyvan

2019

Acta Scientiae. Vet.

View full text Add to dashboard Cite

show abstract

“…Abundance of the aflatoxin‐producing bacteria in soil, as well as their proliferation in decaying vegetation, such as grain or hay stored under warm and moist conditions, results in common food and animal feed contamination. A large point of concern is the aflatoxin transfer to offspring during gestation or lactation, as well as to other species via milk, eggs, or meat …”

Section: Introductionmentioning

confidence: 99%

“…Several other in vivo AFB1 degrading pathways have been proposed, namely epoxidation by the prostaglandin H synthase and lipid peroxidase, whose end products inhibit DNA repair . AFB1 and its metabolite AFM1 have been shown to modulate a large number of proteins involved in important metabolic pathways …”

Section: Introductionmentioning

confidence: 99%

Oxidase or peptidase? A computational insight into a putative aflatoxin oxidase from Armillariella tabescens

Tomin

Tomić

2019

Proteins

View full text Add to dashboard Cite

Aflatoxin oxidase (AFO), an enzyme isolated from Armillariella tabescens, has been reported to degrade aflatoxin B1 (AFB1). However, recent studies reported sequence and structure similarities with the dipeptidyl peptidase III (DPP III) family of enzymes and confirmed peptidase activity toward DPP III substrates. In light of these investigations, an extensive computational study was performed in order to improve understanding of the AFO functions. Steered MD simulations revealed long‐range domain motions described as protein opening, characteristic for DPPs III and necessary for substrate binding. Newly identified open and partially open forms of the enzyme closely resemble those of the human DPP III orthologue. Docking of a synthetic DPP III substrate Arg2‐2‐naphthylamide revealed a binding mode similar to the one found in crystal structures of human DPP III complexes with peptides with the S1 and S2 subsites’ amino acid residues conserved. On the other hand, no energetically favorable AFB1 binding mode was detected, suggesting that aflatoxins are not good substrates of AFO. High plasticity of the zinc ion coordination sphere within the active site, consistent with that of up to date studied DPPs III, was observed as well. A detailed electrostatic analysis of the active site revealed a predominance of negatively charged regions, unsuitable for the binding of the neutral AFB1. The present study is in line with the most recent experimental study on this enzyme, both suggesting that AFO is a typical member of the DPP III family.

show abstract

“…AFM1 is a major metabolite produced by CYP1A2 and is the most carcinogenic of the hydroxylated metabolites. This is supported by the DNA-binding effect of AFM1 which has been demonstrated in rat, mouse, and pig and has even been identified to form an N7-guanine adduct similar to AFB1 [65]. Just like AFB1, AFM1 can be excreted in cattle or human milk [66].…”

Section: The Metabolism and Toxic Mechanism Of Afb1mentioning

confidence: 83%

The Toxic Effects of Aflatoxin B1: An Update

Shan¹

2020

Aflatoxin B1 Occurrence, Detection and Toxicological Effects

View full text Add to dashboard Cite

Aflatoxin B1 (AFB1) is the most toxic in aflatoxin family. It is well known for its involvement in hepatic carcinogenesis. Other adverse effects include immune weakness, reproduction deficiency, malnutrition, and growth impairment. The key mechanism of AFB1 carcinogenesis is supposed to be epoxidation, which produce the AFB1-8,9-epoxide (AFBO) strongly adductive to DNA molecules. Other metabolites like AFM1, AFH1, and AFL, which retain DNA adductive capability, extend its toxicity. Scientists now found that AFB1 also affected epigenetic regulation, which might shed new light into AFB1 toxicity mechanism researches. The detoxification of AFB1 has always been a hot spot in AFB1-related studies. The major methods can be categorized into physical treatment, biological treatment, chemical treatment, combination strategy, and sorbent additives. None of the methods is 100% perfect, however considering economic factors, simplicity, effectiveness, safety, and preservation of the food nutrition. This review will discuss the toxicity and toxic mechanisms of AFB1. Also, detoxification of AFB1 will be reviewed.2 as in the 1970s, its hepatocarcinogenic property has been testified in animal models [5], and there since, several epidemiological studies from Asia and Africa areas monitored intersection of high HCC incidence and AFB1 contamination, with 4.6-28.2% of HCC cases globally attributed to AFB1 exposure [6]. Moreover, hepatitis B virus (HBV) that cooperates with AFB1 can drastically increase the risk of HCC by 30-fold [7]. Recent researches also find evidences that hepatitis C virus (HCV) also has a synergistic role with AFB1 in hepatocarcinogenesis. Jeannot et al. found that the incidence of tumorous or pretumorous lesions was elevated by 2.5-fold in AFB1-treated HCV transgenic mice compared with wild-type mice [8]. Recently, a 20-year clinical follow-up study in Taiwan investigated HCC risk associated with AFB1 exposure in HCV-positive and HBV-HCV-negative individuals. HCV and AFB1 exposure were both found as independent risk factors for HCC development. Elevated serum AFB1albumin adduct levels were significantly associated with an increased risk of HCC newly developed within 8 years of follow-up in non-HBV-non-HCV participants with habitual alcohol consumption [crude OR (95% CI) for high vs. low/undetectable levels, 4.22 (1.16-15.37)], and HCV-infected participants [3.39 (1.31-8.77)], but not in non-HBV-non-HCV participants without alcohol drinking habit. Therefore, it indicated that AFB1 exposure contributes to the development of HCC in participants with significant risk factors for cirrhosis including alcohol and HCV infection [9]. What's more, AFB1 exposure can induce the increased levels of blood glucose in mice and, also, the high probability to develop liver cancer [10].Liver is not the only target organ of AFB1 toxification. Its impairment on the immune system has been established in both humans and animals. Several studies linked AFB1 exposure with reduced levels or functions of immunological factors, such as de...

show abstract

Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

Cited by 360 publications

References 103 publications

Determination of Aflatoxin M1 and Ochratoxin A in Raw, Pasteurized and UHT Milk in Turkey

Determination of Aflatoxin M1 and Ochratoxin A in Raw, Pasteurized and UHT Milk in Turkey

Oxidase or peptidase? A computational insight into a putative aflatoxin oxidase from Armillariella tabescens

The Toxic Effects of Aflatoxin B1: An Update

Contact Info

Product

Resources

About