Maize consumption and circulating aflatoxin levels in Mexican middle- and older-aged adults: A cross-sectional analysis.

Background: Maize is frequently contaminated by aflatoxin B (AFB), an established liver carcinogen.

Objective: To estimate the effect of maize and maize tortilla consumption on AFB-lysine adduct (AFB-lys) concentrations in middle- and older-aged adults living in south and eastern Mexico.

Methods: We conducted a cross-sectional analysis in a representative sample of 915 adults aged ≥40 years living in south and eastern Mexico in 2018-19.

Liver Cancer: Progress and Priorities.

Liver cancer, the sixth most frequently occurring cancer in the world and the third most common cause of cancer mortality, has wide geographical variation in both incidence and mortality rates. At the end of the 20th century, incidence rates began declining in some high-rate areas and increasing in some lower-rate areas. These trends were undoubtedly driven by the shifting contributions of both well-established and more novel risk factors.

Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases.

Mass Spectrometry-Based Method to Measure Aflatoxin B DNA Adducts in Formalin-Fixed Paraffin-Embedded Tissues.

Aflatoxin B (AFB) is a potent human liver carcinogen produced by certain molds, particularly and , which contaminate peanuts, corn, rice, cottonseed, and ground and tree nuts, principally in warm and humid climates. AFB undergoes bioactivation in the liver to produce AFB--8,9-epoxide, which forms the covalently bound cationic AFB-7-guanine (AFB7-Gua) DNA adduct. This adduct is unstable and undergoes base-catalyzed opening of the guanine imidazolium ring to form two ring-opened diastereomeric 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy-aflatoxin B (AFB-FapyGua) adducts.

Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation.

Human tissue three-dimensional (3D) organoid cultures have the potential to reproduce the physiological properties and cellular architecture of the organs from which they are derived. The ability of organoid cultures derived from human stomach, liver, kidney, and colon to metabolically activate three dietary carcinogens, aflatoxin B (AFB), aristolochic acid I (AAI), and 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), was investigated. In each case, the response of a target tissue (liver for AFB; kidney for AAI; colon for PhIP) was compared with that of a nontarget tissue (gastric).

Association of aflatoxin with gallbladder cancer in a case-control study nested within a Chinese cohort.

We evaluated whether aflatoxin B (AFB ) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB -lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986-1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at sample collection, date of blood draw and residence.

Aflatoxin exposure in adults in southern and eastern Mexico in 2018: A descriptive study.

Objective: To estimate the frequency of detection and levels of aflatoxin B-lysine adduct (AFB-lys), an important hepatocellular carcinoma (HCC) risk factor, in eastern and southern Mexico.

Materials And Methods: We determined serum AFB-lys using mass spectrometry in a representative sample of 952 adults (weighted n = 7,493,354) from five states (Campeche, Chiapas, Tamaulipas, Veracruz and Yucatán) in 2018. We calculated overall and subgroup-specific frequency of detection and 95% confidence intervals (95%CI) and median AFB-lys levels and quartiles.

Association of plasma aflatoxin with persistent detection of oncogenic human papillomaviruses in cervical samples from Kenyan women enrolled in a longitudinal study.

Background: Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens.

Global Discovery and Temporal Changes of Human Albumin Modifications by Pan-Protein Adductomics: Initial Application to Air Pollution Exposure.

Assessing personal exposure to environmental toxicants is a critical challenge for predicting disease risk. Previously, using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys and ambient air pollutant levels (Smith et al., .

Association of Plasma Aflatoxin With Persistent Detection of Oncogenic Human Papillomaviruses in Cervical Samples From Kenyan Women Enrolled in a Longitudinal Study.

Background Cervical cancer is common among Kenyan women and is caused by oncogenic human papillomaviruses (HR-HPV). Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of cervical HR-HPV detection.

Mycotoxins were not associated with environmental enteropathy in a cohort of Tanzanian children.

Enteropathy is a pathophysiological condition characterized by decreased intestinal barrier function and absorption. Past studies have hypothesized that mycotoxins might impair children's growth by causing intestinal enteropathy, including interactions between mycotoxins and pathogens. We investigated the association of two mycotoxins, aflatoxin B (AFB ) and fumonisin B (FB ), independently and in conjunction with microbial pathogens, with fecal biomarkers of environmental enteropathy in children.

Circulating bile acid concentrations and non-alcoholic fatty liver disease in Guatemala.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression.

Aims: To characterise the relationship between bile acid levels and NAFLD at the population level METHODS: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center.

Materials And Methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center.

Assessing the Validity of Normalizing Aflatoxin B-Lysine Albumin Adduct Biomarker Measurements to Total Serum Albumin Concentration across Multiple Human Population Studies.

The assessment of aflatoxin B (AFB) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring of AFB exposure. To compare samples across different individuals and settings, the conventional practice has involved the normalization of raw AFB-lysine adduct concentrations (e.g.

Associations between aflatoxin B-albumin adduct levels with metabolic conditions in Guatemala: A cross-sectional study.

Background And Aims: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B (AFB) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB also contributes to the high prevalence of the metabolic disorders has not been previously examined.

Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B Exposure in 828 Mother-Child Dyads from Bangladesh and Malawi.

Background: In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation.

Objectives: Aflatoxin exposure and selected determinants thereof were characterized in mother-child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh.

Methods: Circulating aflatoxin B (AFB)-lysine albumin adducts were measured in dyads from Bangladesh (= 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (= 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry.

Aflatoxin and the Etiology of Liver Cancer and Its Implications for Guatemala.

During the 60 years since the first scientific reports about a relation between aflatoxin exposure and adverse health consequences, both in animals and humans, there has been a remarkable number of basic, clinical and population science studies characterizing the impact of this mycotoxin on diseases such as liver cancer. Many of these human investigations to date have focused on populations residing in Asia and Africa due to the high incidence of liver cancer and high exposures to aflatoxin. These studies formed the basis for the International Agency for Research on Cancer to classify the aflatoxins as Group 1 known human carcinogens.

Environmental Pollutants, Mucosal Barriers, and Pathogen Susceptibility; The Case for Aflatoxin B as a Risk Factor for HIV Transmission and Pathogenesis.

HIV transmission risk is dependent on the infectivity of the HIV+ partner and personal susceptibility risk factors of the HIV- partner. The mucosal barrier, as the internal gatekeeper between environment and self, concentrates and modulates the internalization of ingested pathogens and pollutants. In this review, we summarize the localized effects of HIV and dietary toxin aflatoxin B1 (AFB), a common pollutant in high HIV burden regions, e.

Cyclohexanone Exposure in Children on Extracorporeal Membrane Oxygenation Support.

The aim of this study was to determine if plasma cyclohexanone and metabolites are associated with clinical outcomes of children on extracorporeal membrane oxygenation (ECMO) support. We performed a secondary analysis of a prospective observational study of children on ECMO support at two academic centers between July 2010 and June 2015. We measured plasma cyclohexanone and metabolites on the first and last days of ECMO support.

Biomonitoring of Ambient Outdoor Air Pollutant Exposure in Humans Using Targeted Serum Albumin Adductomics.

Outdoor air pollution, a spatially and temporally complex mixture, is a human carcinogen. However, ambient measurements may not reflect subject-level exposures, personal monitors do not assess internal dose, and spot assessments of urinary biomarkers may not recapitulate chronic exposures. Nucleophilic sites in serum albumin-particularly the free thiol at Cys-form adducts with electrophiles.