PAH exposure in a Ghanaian population at high risk for aflatoxicosis

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Abstract

It was postulated that a population in sub-Saharan Africa, known to be at high risk for aflatoxicosis due to frequent ingestion of aflatoxin (AF)-contaminated foods could also be exposed to polycyclic aromatic hydrocarbons (PAHs) from a variety of environmental sources. Previously, participants in this population were shown to be highly exposed to AFs, and this exposure was significantly reduced by intervention with NovaSil clay (NS). Objectives of this study were 1) to assess PAH exposure in participants from the AF study using urinary biomarker 1-hydroxypyrene (1-OHP); 2) examine the effect of NS clay and placebo (cellulose) treatment on 1-OHP levels; and 3) determine potential association(s) between AF and PAH exposures. A clinical trial was conducted in 177 Ghanaians who received either NS capsules as high dose or low dose, or placebo (cellulose) for a period of 3 months. At the start and end of the study, urine samples were analyzed for 1-OHP. Of the 279 total samples, 98.9% had detectable levels of 1-OHP. Median 1-OHP excretion in nonsmokers was 0.64 µmol/mol creatinine at baseline and 0.69 µmol/mol creatinine after 3 months. Samples collected at both time points did not show significant differences between placebo and NS-treated groups. There was no linear correlation between 1-OHP and AF-albumin adduct levels. Results show that this population is highly exposed to PAHs (and AFs), that NS and cellulose treatment had no statistically significant effect on 1-OHP levels, and that this urinary biomarker was not linearly related with AF exposure.

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are unavoidable environmental pollutants produced from the incomplete combustion of organic material and are detected in contaminated air, tobacco smoke, and charcoal-grilled and smoked foods (Nikolaou et al., 1984). A variety of PAHs, which normally exist in complex mixtures, have been recognized as carcinogenic (IARC, 1987). The association between high PAH exposure and the risk of lung cancer has been established through various molecular epidemiological studies (Tang et al., 1995, Mastrangelo et al., 1996). It has been documented that PAHs cause cellular and humoral immunotoxicity in vitro and in vivo (White, 1986); additionally, this class of compounds has been shown to cause complex effects on the immune system in humans (Davila et al., 1996, Burchiel and Luster, 2001). The urinary metabolite 1-hydroxypyrene (1-OHP) has been extensively characterized and validated as a biological indicator of PAH exposure in many human populations and is widely accepted due to the presence of pyrene in most PAH mixtures (Levin, 1995, Bouchard and Viau, 1999). While researchers consider urinary metabolites of additional PAHs to be valid, 1-OHP remains the most comprehensively studied biomarker in the urine. Increased levels of 1-OHP excreted in human urine have shown significant correlation with subjects exposed to mixtures of PAHs. The excretion of 1-OHP represents recent PAH exposure with ranges of half-life values reported to be: 24 to 48 h, 6 to 35 h, and 16 to 20 h (Jongeneelen et al., 1990, Buchet et al., 1992). Hence, 1-OHP is used as a short-term biomarker of PAH exposure.

In the Ashanti Region of Ghana, West Africa, human exposure to PAHs may readily occur from a variety of environmental sources as well as preparation of foods by smoking (and subsequent ingestion). Traditional methods of cooking in the region include the use of fire pits and indoor wood-burning stoves; often the dwellings are not well-ventilated. Furthermore, the direct drying and/or smoking of maize, a staple crop in the region, is frequently employed before storage as a means to repel insects. In this same region of Ghana, we have recently shown that people were highly exposed to aflatoxins (AFs) based on biomarkers in urine and blood (Jolly et al., 2006). AFs are naturally occurring metabolites from Aspergillus fungi that are frequently found as contaminants of commodities such as cereal grains, peanuts and tree nuts (CAST, 2003). It has been well-documented that exposure to the most potent congener (AFB1) can cause hepatotoxicity, suppression of the immune system, and anti-nutritional effects in animals and humans (Gong et al., 2002, Turner et al., 2003, Jiang et al., 2007). Chronic exposure to AFs is implicated as a major risk factor in the etiology of hepatocellular carcinoma (HCC), particularly in tropical areas of Southeast Asia, South America, and the sub-Saharan regions of Africa (Wogan, 1992, CAST, 2003). Additionally, it is estimated that 80% of all HCC cases occur in developing countries (Wild and Hall, 2000).

In West Africa, the risk of developing HCC is significantly increased by infection with hepatitis B virus (HBV). Epidemiological studies and animal models have demonstrated synergistic interactions between AF exposure and HBV infection in the development of HCC (Turner et al., 2002). In a recent community-based cohort study conducted in Taiwan, an increased risk of HCC was associated with PAH exposure, while an even greater risk was found among participants who were also exposed to high levels of AFs (Wu et al., 2007). Thus, strategies that reduce multiple exposures to AFs and PAHs are highly desirable for populations at risk for both agents. One PAH, benzo[a]pyrene (BaP), is similar to AFB1 in that: 1) both AFB1 and BaP are carcinogens, 2) their mutagenic action requires metabolic activation to epoxide analogs (BaP 7,8-diol-9,10-epoxide and AFB1 exo-8,9-epoxide), and 3) their ability to form DNA adducts primarily at the N-2 and N-7 position of the guanine residue, respectively, can lead to tumorigenesis. Among various strategies used to reduce exposures, binding of toxin by NovaSil (NS), a montmorillonite clay, in the gastrointestinal tract (enterosorption) appears to be a safe and viable approach for AFs (Phillips et al., 2007). This conclusion is based on previous studies using multiple animal models and clinical intervention trials in humans in the U.S. and Ghana (Wang et al., 2005, Afriyie-Gyawu et al., 2008). Although, no clinical interventions have been reported for PAHs using enterosorbent strategies, Viau et al. (2004) noted a trend in the reduction of urinary excretion of 1-OHP in rats fed pyrene and diets containing fiber. Additionally, bulk cellulose in the diet was shown to affect the recovery of 1-OHP from the urine suggesting that it may bind PAHs. Therefore, the main objectives of this study were to assess the overall exposure to PAHs in our population in Ghana by measuring 1-OHP and to determine if there was a relationship between AF and PAH exposures. Another objective was to determine the effect of NS versus placebo (cellulose) treatment on 1-OHP levels.

Section snippets

Materials

Authentic 1-OHP reference standard was obtained from the Midwest Research Institute, Chemical Carcinogen Reference Standard Repository (Kansas City, MO). Sep-Pak C18 cartridges were purchased from Waters (Milford, MA). HPLC-grade solvents and β-glucuronidase from Helix pomatia (type HP-2S) were obtained from Sigma-Aldrich Chemical Co. (St. Louis, MO). All of the experiments were done using filtered and deionized water (18.2 MΩ.cm) (Millipore, Milford, MA). The NS clay was supplied by Engelhard

Results

A sum of 162 out of 177 participants (91.5%) that began the clinical trial completed the 3-month period. A total of 279 urine samples collected at baseline and after 3 months of NS intervention were analyzed for urinary 1-OHP. Out of the total urines, 98.9% showed detectable levels of 1-OHP. Median, mean ± SD, and the range of 1-OHP levels at both time points are presented in Table 1; participants are further delineated as smokers or non-smokers. Since the data was not normally distributed,

Discussion

Results illustrate that the majority of the study population had a measurable exposure to PAHs. 1-OHP levels measured in this Ghanaian population were higher than those previously recorded for non-smoking individuals in numerous countries. For instance, the median 1-OHP level measured in non-smokers at baseline in our study population (0.64 µmol/mol Cr) is considerably higher than median 1-OHP concentrations measured in non-smokers from the US (0.27 µmol/mol Cr) and Canada (0.07 µmol/mol Cr) (

Acknowledgements

We gratefully acknowledge the on-site physicians, technicians and other health personnel at the Ejura District Hospital. We thank all volunteers whose participation made this study possible. This work was supported by the United States Agency for International Development (USAID LAG-G-00-96-90013-00) through Peanut CRSP of the University of Georgia.

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  • Cited by (0)

    1

    Present address: Jian-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA 30460, USA.

    2

    Present address: Department of Environmental Health Science, College of Public Health, The University of Georgia, Athens GA 30602, USA.

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