fumonisin-b1 and Esophageal-Neoplasms

Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB(1)-contaminated maize-based food. However, possible involvement of FB(1) in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB(1) as a possible carcinogen to humans (group 2B). FB(1) is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB(1) toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB(1) has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB(1) neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.

Topics: Animals; Carcinogens; Cell Culture Techniques; Disease Models, Animal; Esophageal Neoplasms; Food Contamination; Food Microbiology; Fumonisins; Fusarium; Humans; Leukoencephalopathies; Liver Neoplasms; Neural Tube Defects; Neurotoxins; Neurotransmitter Agents; Pulmonary Edema; Zea mays

The rates of cell proliferation and cell loss in conjunction with the differentiation status of a tissue are among the many factors contributing to carcinogenesis. Nongenotoxic (non-DNA reactive) chemicals may affect this balance by increasing proliferation through direct mitogenesis or through a regenerative response following loss of cells through cytotoxic (oncotic) or apoptotic necrosis. In a recent NTP study in Fischer rats and B6C3F(1) mice, the mycotoxin fumonisin B(1) caused renal carcinomas in male rats and liver cancer in female mice. In an earlier study in male BD-IX rats, fumonisin B(1) caused hepatic toxicity and hepatocellular carcinomas. An early effect of fumonisin B(1) exposure in these target organs is apoptosis. However, there is also some evidence of oncotic necrosis following fumonisin B(1) administration, especially in the liver. Induction of apoptosis may be a consequence of ceramide synthase inhibition and disruption of sphingolipid metabolism by fumonisin B(1). Fumonisin B(1) is not genotoxic in bacterial mutagenesis screens or in the rat liver unscheduled DNA-synthesis assay. Fumonisin B(1) may be the first example of an apparently nongenotoxic (non-DNA reactive) agent producing tumors through a mode of action involving apoptotic necrosis, atrophy, and consequent regeneration.

Topics: Africa; Animals; Apoptosis; Carboxylic Acids; China; Decision Making; DNA; Esophageal Neoplasms; Female; Fumonisins; Humans; Kidney; Kidney Neoplasms; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred Strains; Mycotoxins; Rats; Rats, Inbred Strains; Risk Factors; Sphingolipids

Fumonisins, fungal toxins produced by Fusarium moniliforme, contaminate maize based foods and feeds throughout the world. They cause liver and kidney toxicity in animals in addition to leukoencephalomalacia in horses and pulmonary edema in pigs. Fumonisin B(1) is carcinogenic in rats and mice. Ecological studies have linked consumption of fumonisin contaminated maize with oesophageal cancer in human populations in South Africa and China. This review discusses the potential health risks for people exposed to the fumonisins, and describes how mechanistic studies of toxicity in animal models have allowed the development of putative biomarkers of fumonisin exposure at the individual level. The requirements for an applicable biomarker include sample availability as well as a high specificity and sensitivity for the exposure of interest. Most environmental toxic insults involve complex exposures both to other toxins and to infections; these confounding factors need to be considered in assessing both the validity of the biomarker and the exposure-disease associations. Fumonisins can be detected in the urine of animals in feeding studies but the sensitivity of the current methodology means only highly exposed people could be monitored. Mechanistic studies indicate that ceramide synthase, an enzyme involved in sphingolipid synthesis, is one cellular target for fumonisin toxicity and carcinogenicity, and this disruption to sphingolipid metabolism increases the ratio of two sphingoid precursors, sphinganine and sphingosine. The altered ratio has been observed in tissues, serum and urine for a number of animal models suggesting it as a good candidate marker of fumonisin exposure. Despite development of analytical methods to measure this biomarker there have been no studies to date correlating it to fumonisin intake in people. Given the toxic effects of fumonisins in animals and the widespread human exposure, which has been calculated to reach 440 micrograms kg(-1) body weight day(-1) in a population consuming high quantities (460 g day(-1)) of contaminated maize, then the development of biomarkers and their application in epidemiological studies should be a priority for research on these toxins.

Topics: Animals; Biomarkers; Carboxylic Acids; Carcinogens, Environmental; Carcinoma, Hepatocellular; Esophageal Neoplasms; Female; Food Contamination; Food Microbiology; Fumonisins; Humans; Liver Neoplasms; Male; Mice; Neoplasms, Experimental; Rats; Risk Assessment; Sphingolipids; Sphingosine

The fumonisins (FBs) are a group of closely related mycotoxins that are prevalent in maize. They were isolated from strains of Fusarium moniliforme (Sheldon), which were implicated in the aetiology of human oesophageal cancer in the Transkei, South Africa. Their discovery explained the cause of equine encephalomalacia, or "hole in the head" syndrome, when it was found by feeding trials in horses that they elicited the disease. Subsequently, they were found to cause hepatic cancer in rats and pulmonary oedema in pigs, with most animal species tested showing liver and kidney damage. FB1 is the most important of the group and, although poorly absorbed from the gastrointestinal tract, its action is at the cellular level, affecting sphingolipid metabolism. Ceramides derived from sphingosine metabolism are cell regulatory factors affecting, among other things, DNA synthesis. Because FB1 has a close molecular resemblance to sphinganine, it interferes with ceramide biosynthesis and, hence, the processes that it regulates, which is thought to explain its carcinogenic properties. Studies on the FBs are still at a relatively early stage, but it is already clear that they play an important role in animal mycotoxicoses and, by implication, in human disease. A more positive aspect is that they will be used in elucidating the role of sphingolipids in cellular regulation.

Topics: Animal Diseases; Animals; Carcinogens, Environmental; Esophageal Neoplasms; Fumonisins; Fusarium; Humans; Molecular Structure; Mycotoxins

Fusarium moniliforme Sheldon occurs worldwide on corn intended for human and animal consumption. A closely related species Fusarium proliferatum also occurs frequently on corn. Yellow dent corn, white dent corn, white and yellow popcorn and sweet corn may be contaminated. Both organisms are capable of producing fumonisins, including Fumonisin B1 (FB1), Fumonisin B2 (FB2) and Fumonisin B3 (FB3). Fumonisins have been found in corn and corn based foods worldwide. Fumonisins may be found in sound whole kernel corn at levels at or below 1.0 microgram/g. By contrast animal disease problems begin to occur at fumonisin levels above 5.0 to 10.0 micrograms/g. Corn based food products that have the most frequent and highest fumonisin levels, besides whole kernel corn, are corn meal, corn flour and corn grits. In the U.S., corn meal and flour have been found contaminated with FB1 at levels from 0.5 to 2.05 micrograms/g, and grits from 0.14 to 0.27 microgram/g. Corn flakes, corn pops, corn chips and tortilla chips have typically been found negative when tested for fumonisins. Popcorn, sweet corn and hominy corn have been found contaminated with sporadic, low levels (0.01 to 0.08 microgram/g) of fumonisins. Contamination levels of corn based foods in Europe appear to be similar to slightly lower than similar products in the U.S., with the possible exception of Italy, where their corn hybrids and corn-based foods appear to be more frequently contaminated with higher levels of fumonisins.

Topics: Animals; Carcinogens, Environmental; Esophageal Neoplasms; Food Contamination; Food Microbiology; Fumonisins; Fusarium; Humans; Mycotoxins; Zea mays

Topics: Animals; Carcinogens, Environmental; Edible Grain; Esophageal Neoplasms; Food Analysis; Food Contamination; Fumonisins; Humans; Mycotoxins; Polyenes

Contamination of corn with the fungus Fusarium moniliforme and its secondary metabolites, the fumonisins, has been associated with several human and animal diseases. This paper summarizes present knowledge and presents new data on the levels of fumonisins present in foods and feeds associated with these diseases as well as in commercial corn and corn-based products. The doses of fumonisins to which humans and animals consuming these products would be exposed are compared with those doses known to produce LEM in horses and hepatocarcinogenesis in rats. It is concluded that the known naturally occurring levels of fumonisins present a potential threat to human and animal health and realistic tolerance levels need to be set.

Topics: Animal Feed; Animals; Carcinogens, Environmental; Encephalomalacia; Esophageal Neoplasms; Food Microbiology; Fumonisins; Fusarium; Horse Diseases; Horses; Humans; Liver Neoplasms, Experimental; Mycotoxins; Zea mays

In the Centane magisterial area of South Africa, high rates of oesophageal cancer have been associated with home-grown maize contaminated with fumonisins. The aim of this study was to implement a simple intervention method to reduce fumonisin exposure in a subsistence-farming community. The hand-sorting and washing procedures, based on traditional maize-based food preparation practices, were previously customised under laboratory-controlled conditions. Home-grown maize and maize-based porridge collected at baseline were analysed for fumonisin B(1), B(2) and B(3). The geometric mean (95% confidence interval) of fumonisin contamination in the home-grown maize at baseline was 1.67 (1.21-2.32) mg kg(-1) and 1.24 (0.75-2.04) mg kg(-1) (dry weight) in the porridge. Fumonisin exposure was based on individual stiff porridge consumption and the specific fumonisin levels in the porridge (dry weight) consumed. Porridge (dry weight) consumption at baseline was 0.34 kg day(-1) and fumonisin exposure was 6.73 (3.90-11.6) µg kg(-1) body weight day(-1). Female participants (n = 22) were trained to recognise and remove visibly infected/damaged kernels and to wash the remaining maize kernels. The discarded kernels represented 3.9% by weight and the fumonisins varied from 17.1 to 76.9 mg kg(-1). The customised hand-sorting and washing procedures reduced fumonisin contamination in the maize and porridge by 84 and 65%, respectively. The intervention reduced fumonisin exposure by 62% to 2.55 (1.94-3.35) µg kg(-1) body weight day(-1). This simple intervention method has the potential to improve food safety and health in subsistence-farming communities consuming fumonisin-contaminated maize as their staple diet.

Topics: Adolescent; Adult; Aged; Esophageal Neoplasms; Female; Food Contamination; Food Handling; Food Inspection; Fumonisins; Humans; Middle Aged; Patient Education as Topic; Rural Health; Seeds; South Africa; Young Adult; Zea mays

Fumonisin B1 (FB1) is a mycotoxin frequently found in agricultural commodities. The toxin poses a considerable risk for human and animal health. FB1 is among several mycotoxins produced by Fusarium spp. contaminating virtually any cereal and other Poaceae. Their intracellular action includes the promotion of oxidative stress through the generation of reactive oxygen species (ROS) that damage biomolecules such as DNA. These toxic effects were observed in vivo and in vitro. However, the association between esophageal lesions and oxidative stress induced by FB1. Studies in China, Iran and South Africa showed higher exposure to fumonisins in areas with higher risk of esophageal cancer (EC). Exposure to mycotoxins may be inevitable in Mozambique. How mycotoxins, particularly fumonisins from the contaminated food, can be associated with the emergence of EC in Mozambique? Herein, we revise the literature and present some pieces of evidence in order to highlight the burden of mycotoxins and to provide evidence-based considerations for the stakeholders involved in the management of the EC agenda in Mozambique. The information presented herein supports the need to implement novel and/or to revisit the existent detoxification methods to reduce the global burden of mycotoxins and its outcomes in health management.

Topics: Animals; Carcinogens, Environmental; Esophageal Neoplasms; Food Contamination; Fumonisins; Fusarium; Humans; Mozambique; Mycotoxins; Oxidative Stress; Reactive Oxygen Species

Fumonisin B

Topics: Adenosine Triphosphate; Cell Line, Tumor; Esophageal Neoplasms; Fumonisins; Glutathione; Humans; Lipid Peroxidation; Malondialdehyde; Membrane Potential, Mitochondrial; Oxidative Stress; Reactive Oxygen Species

Fumonisin B1 (FB1) is a toxic and carcinogenic mycotoxin produced in cereals due to fungal infection. This study was conducted to determine FB1 contamination of rice and corn samples and its relationship with the rate of esophageal cancer (EC) in a high risk area in northeastern Iran.. In total, 66 rice and 66 corn samples were collected from 22 geographical subdivisions of Golestan province of Iran. The levels of FB1 were measured for each subdivision by thin layer and high pressure liquid chromatographies. The mean level of FB1 and the proportions of FB1 contaminated samples were compared between low and high EC-risk areas of the province.. The mean of FB1 levels in corn and rice samples were 223.6 and 21.6 μg/g, respectively. FB1 contamination was found in 50% and 40.9% of corn and rice samples, respectively. FB1 level was significantly higher in rice samples obtained from high EC-risk area (43.8 μg/g) than those obtained from low risk area (8.93 μg/g) (p-value=0.01). The proportion of FB1 contaminated rice samples was also significantly greater in high (75%) than low (21.4%) EC-risk areas (p-value=0.02).. We found high levels of FB1 contamination in corn and rice samples from Golestan province of Iran, with a significant positive relationship between FB1 contamination in rice and the risk of EC. Therefore, fumonisin contamination in commonly used staple foods, especially rice, may be considered as a potential risk factor for EC in this high risk region.

Topics: Edible Grain; Esophageal Neoplasms; Food Contamination; Fumonisins; Humans; Iran; Mycotoxins; Oryza; Risk; Zea mays

Aflatoxins and fumonisins are ubiquitous foodborne toxicants and the co-occurrence of these mycotoxins in human foods represents a significant public health concern, which has been strongly associated with human aflatoxicosis, neural tube defects, as well as many types of primary cancers. In this study the co-contamination of aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)) in food and human dietary exposure was investigated in residents of three different areas of China. A total of 209 food samples were measured for AFB(1) and FB(1). The median AFB(1) levels were 13.5, 2.3 and 1.3 µg kg(-1) and the median FB(1) levels were 2.6, 0.4 and 0.3 mg kg(-1) in corn samples collected from Huaian (a high-risk area for oesophageal cancer), Fusui (a high-risk area for liver cancer) and Huantai (a low-risk area for both oesophageal and liver cancers), respectively. The median level of AFB(1) in plant oil of Fusui was the highest (52.3 µg kg(-1)) among all food samples analysed. Co-contamination of these two mycotoxins was found in corn, rice and wheat flour. Based on measured food consumption data, the averaged daily dietary intake of AFB(1) was 0.397 µg (range = 0.269-1.218 µg) in residents of Huantai, 1.723 µg (0.224-49.772 µg) in Huaian, and 2.685 µg (1.006-14.534 µg) in Fusui. The averaged FB(1) daily dietary intake was 92.4 µg (range = 55.0-362.1 µg) for residents of Huantai, 460.0 µg (83.2-2894.5 µg) in Huaian, and 138.6 µg (30.0-10,541.6 µg) in Fusui. These data suggest that the co-exposure to AFB(1) and FB(1) in residents of rural China may contribute to the aetiology of human chronic diseases in high-risk areas.

Topics: Adult; Aflatoxin B1; Aged; Carcinogens, Environmental; China; Diet; Esophageal Neoplasms; Female; Flour; Food Contamination; Fumonisins; Humans; Liver Neoplasms; Male; Middle Aged; Oryza; Plant Extracts; Risk Factors; Seeds; Surveys and Questionnaires; Zea mays

The consumption of maize highly contaminated with carcinogenic fumonisins has been linked to high oesophageal cancer rates. The aim of this study was to validate a urinary fumonisin B1 (UFB1) biomarker as a measure of fumonisin exposure and to investigate the reduction in exposure following a simple and culturally acceptable intervention.. At baseline home-grown maize, maize-based porridge, and first-void urine samples were collected from female participants (n=22), following their traditional food practices in Centane, South Africa. During intervention the participants were trained to recognize and remove visibly infected kernels, and to wash the remaining kernels. Participants consumed the porridge prepared from the sorted and washed maize on each day of the two-day intervention. Porridge, maize, and urine samples were collected for FB1 analyses.. The geometric mean (95% confidence interval) for FB1 exposure based on porridge (dry weight) consumption at baseline and following intervention was 4.84 (2.87-8.14) and 1.87 (1.40-2.51) μg FB1/kg body weight/day, respectively, (62% reduction, P<0.05). UFB1C, UFB1 normalized for creatinine, was reduced from 470 (295-750) at baseline to 279 (202-386) pg/mg creatinine following intervention (41% reduction, P=0.06). The UFB1C biomarker was positively correlated with FB1 intake at the individual level (r=0.4972, P<0.01). Urinary excretion of FB1 was estimated to be 0.075% (0.054%-0.104%) of the FB1 intake.. UFB1 reflects individual FB1 exposure and thus represents a valuable biomarker for future fumonisin risk assessment.. The simple intervention method, hand sorting and washing, could positively impact on food safety and health in communities exposed to fumonisins.

Topics: Adult; Aged; Biomarkers; Carcinogens, Environmental; Esophageal Neoplasms; Female; Food Contamination; Fumonisins; Humans; Middle Aged; South Africa; Young Adult; Zea mays

Levels of serum and urinary sphinganine (Sa) and sphingosine (So), the Sa/So ratio, and urinary-free fumonisin B(1) (FB(1)) were determined in a cross-sectional study consisting of 43 adults in Huaian and 34 adults in Fusui, China. Home-produced corn had 100% contamination with FB(1). There were 93.0% (40/43) of Huaian subjects and 52.9% (18/34) of Fusui subjects with daily FB(1) intakes greater than 2 microg kg(-1) body weight, which showed a significant difference (p < 0.01). Levels of sphinganine and sphingosine and the Sa/So ratio were not correlated with levels of dietary exposure. The median level of the serum Sa/So ratio in Huaian subjects (0.41, range = 0.14-0.85) was significantly lower than that in Fusui subjects (0.78, range = 0.57-1.08) (p < 0.01). The median level of the urinary Sa/So ratio was also significantly lower in Huaian subjects (0.31, range = 0.08-1.33) than in Fusui subjects (0.57, range = 0.03-2.52) (p < 0.01). Urinary-free FB(1) was detected in 83.7% (36/43) of Huaian samples and in 82.4% (28/34) of Fusui urine samples (p > 0.05). However, the median level of urinary-free FB(1) in Huaian subjects, 3.91 (range = 0.06-253.61) ng mg(-1) creatinine, was significantly higher than 0.39 (range = 0.01-3.72) ng mg(-1) creatinine found in Fusui subjects (p < 0.01). These results suggest that urinary-free FB(1) may be a potential biomarker for human fumonisin exposure, while further validation is needed in human epidemiological and intervention studies.

Topics: Adult; Biomarkers; China; Cross-Sectional Studies; Diet; Esophageal Neoplasms; Female; Food Analysis; Food Contamination; Foodborne Diseases; Fumonisins; Humans; Incidence; Liver Neoplasms; Male; Middle Aged; Risk Factors; Seeds; Sphingosine; Zea mays

Fumonisin B(1) (FB(1)) is the most abundant of the fumonisin mycotoxins, mainly produced in maize by F. verticillioides and F. proliferatum. A total of 282 corn samples harvested in 2005 from six provinces, the main corn-producing areas of China, were analyzed for FB(1) using high-performance liquid chromatography. All samples except one were (99.6%) positive for FB(1) at levels varying from 3 to 71,121 ng/g with mean and median levels for all samples of 6,662 and 1,569 ng/g, respectively. During an analysis of the distribution pattern for FB(1), it became apparent that 43.6% of tested samples had FB(1) concentrations below 1,000 ng/g, while 25.2% contained in excess of 5,000 ng/g. The average exposure to FB(1) (1.1 microg/kg body weight/day) is within the provisional maximum tolerable daily intake of 2 microg/kg body weight/day set by the Joint FAO/WHO Expert Committee on Food Additives.

Topics: Carcinogens, Environmental; China; Chromatography, High Pressure Liquid; Esophageal Neoplasms; Food Microbiology; Food Supply; Fumonisins; Fusarium; Humans; Zea mays

Fumonisin B1 and ochratoxin A are mycotoxins of importance to public health and agro-economics. Although much is known about their cellular toxicity and carcinogenesis in animals, there are no reports of adverse effects on immune cells (leukocytes) or on the immune modulation of the molecular messengers (cytokines) in humans. This study was designed, therefore, to determine and compare the morphological effects of fumonisin B1 and ochratoxin A on lymphocytes and neutrophils harvested from the circulation of healthy volunteer subjects and patients with oesophageal and breast carcinomas. Both fumonisin B1 and ochratoxin A reduced the number of viable lymphocytes and neutrophils harvested from the circulation of volunteer subjects carcinoma patients in a dose-dependent manner. Leukocyte secretion of cytokines on exposure to the mycotoxins was evaluated by immunocytochemical methods. Expression of granulocyte-colony stimulating factor (G-CSF), tumour necrosis factor (TNF-alpha) and chemokine (CX3CR1) receptors were determined on the circulating leukocytes and the immunolabelling visualized by brightfield-and electron-microscopy. Cytokine levels were determined in the circulation of healthy volunteer subjects and in patients with oesophageal and breast carcinomas since they reflect the status of the immune system in humans. The findings of this study on immunocytes (leukocytes) and the immune molecular messengers (cytokines) suggest that fumonisin B1 and ochratoxin A have an immuno-suppressive effect in humans, in particular patients with cancer by impairing immune surveillance.

Topics: Adult; Aged; Breast Neoplasms; CX3C Chemokine Receptor 1; Cytokines; Esophageal Neoplasms; Female; Fumonisins; Granulocyte Colony-Stimulating Factor; Humans; Leukocytes; Male; Microscopy, Electron, Transmission; Middle Aged; Neutrophils; Ochratoxins; Receptors, Chemokine; Receptors, Granulocyte Colony-Stimulating Factor; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

Fumonisin B1 (FB1) is reportedly the causative agent of several animal mycotoxicoses and has etiologically been linked to human oesophageal and liver cancer in certain areas of South Africa and China. To study a possible relationship between exposure to FB1 and human cancer risk, the current status of FB1 contamination in food samples in Huaian and Fusui, where incidences of oesophageal and liver cancer are amongst the highest in China, was investigated. A total of 259 corn samples were collected from individual households in five villages of different townships in Huaian during December 2001 and December 2002, and in four villages of different townships in Fusui during May 2001 and May 2002. Corn samples were also collected from individual households in two villages in Huantai, an area with low incidences of both cancers. Enzyme-linked immunosorbent assays (ELISA) and immunoaffinity-HPLC methods were used for FB1 analysis. In corn samples from Huaian, FB1 was detectable in 95.7% (112/117) of the samples, with an average of 2.84 mg kg-1 (range 0.1-25.5 mg kg-1). FB1 was detected in 83.0% (78/94) of the Fusui samples, with an average of 1.27 mg kg-1 (range 0.1-14.9 mg kg-1), and in 83.3% (40/48) of Huantai samples, with an average of 0.65 mg kg-1 ranging from 0.1 to 5.7 mg kg-1. The level of FB1 in corn samples from Huaian was significantly higher than from Huantai (P < 0.001). In addition, 47 of 112 (42.0%) positive Huaian samples had FB1 level greater than 2.0 mg kg-1, which was significantly higher than 10.0% (4/40) of Huantai samples (P < 0.001). Furthermore, variations were found between samples collected in different years and different villages. The high contamination rates of FB1 found in food from these areas, along with previous reports, suggest a possible contributing role of FB1 in human esophageal- and hepato-carcinogenesis.

Topics: Animals; China; Edible Grain; Esophageal Neoplasms; Food Contamination; Fumonisins; Humans; Liver Neoplasms; Mycotoxins; Risk Factors

In Brazil, the southern region has the highest incidence of esophageal cancer and also the highest production and consumption of corn (Zea mays) products. Corn samples intended for human consumption from the western, northern, and southern regions of the state of Santa Catarina, southern Brazil, had mean total fumonisin B (B(1), B(2), and B(3)) levels of 3.2, 3.4, and 1.7 mg/kg, respectively. Fusarium verticillioides, the predominant fungus in the corn samples, had mean incidences (percent of kernels infected) of 14, 11, and 18% for the three regions, respectively. Additional corn samples intended for animal feed from the southern region had a mean total fumonisin level of 1.5 mg/kg and a mean F. verticillioides incidence of 10%. The fumonisin levels in corn from the state of Santa Catarina, Brazil, were similar to the high levels determined in other high esophageal cancer incidence regions of the world.

Topics: Animal Feed; Animals; Brazil; Esophageal Neoplasms; Food Contamination; Fumonisins; Fusarium; Humans; Zea mays

The fumonisin B(1) (FB(1)) contamination of maize collected in two areas of Iran during 1999 was determined. The 20 maize samples from Mazandaran Province, situated on the Caspian littoral of Iran, consisted of random samples of farmers' lots and were all contaminated with FB(1) at a mean level of 3.18 mg kg(-1) (range 0.68-7.66 mg kg(-1)). The 10 samples (of the same maize cultivar) from Isfahan Province in central Iran were purchased as maize cobs in local retail markets and had mean FB levels of 0.22 mg kg(-1) (mean of all samples, 6/10 samples positive, range <0.01-0.88 mg kg(-1)). The FB levels in Mazandaran, an area of high oesophageal cancer, were significantly (p < 0.0001) higher than the FB levels found in maize from Isfahan, an area of low oesophageal cancer in Iran.

Topics: Carboxylic Acids; Carcinogens, Environmental; Esophageal Neoplasms; Female; Food Contamination; Fumonisins; Humans; Incidence; Iran; Male; Zea mays

Mycotoxins that commonly contaminate staple food grains pose a health hazard to animals and humans. Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, causes equine leukoencephalomalacia and porcine pulmonary edema and has been implicated in the etiology of esophageal cancer (EC) in the Transkei, South Africa. Various studies have indicated that nitrosamines induce EC, and F. verticillioides enhancement of nitrosamine-induced EC in rats has been reported. Dietary catechol (CAT), a constituent of cigarette smoke, was previously found to be a cocarcinogen with methyl-N-nitrosamine for inducing esophageal tumors in rats. In the present study we therefore investigated the cytotoxic effects of FB1, diethylnitrosamine (DEN), and CAT on a human esophageal epithelial cell line (SNO) using the methylthiazol tetrazolium assay. For each treatment, toxin concentrations ranged from 2.165 to 34.64 micro M. The results showed that the cytotoxic response of SNO cells was highest in cells treated with 34.64 micro M FB1. SNO cells treated with DEN + FB1 showed greater cytotoxicity than did cells treated with FB1 alone, whereas FB1 appeared to inhibit the cytotoxic effect exerted by CAT alone. The results of this study provide further evidence for the involvement of FB1 in the etiology of esophageal carcinoma.

Topics: Alkylating Agents; Carboxylic Acids; Carcinogens, Environmental; Catechols; Cell Transformation, Neoplastic; Diethylnitrosamine; Dose-Response Relationship, Drug; Epithelial Cells; Esophageal Neoplasms; Esophagus; Fumonisins; Humans; Tumor Cells, Cultured

To explore the correlation between fumonisins and human esophageal cancer (HEC), the estimated fumonisin intake and the urinary sphinganine/sphingosine (Sa/So) ratio were investigated in the population with a high HEC incidence in the suburb of Hebi city, Henan province. Fumonisins were detected from 95 percent of corn samples in the endemic area, and the concentration of total fumonisins (fumonisin B1, B2 and B3) was in the range from 7.2 to 726.8 micrograms/kg. The estimated daily intake of fumonisins was in the range from 0 to 4.84 micrograms/(kg.d) in males, while from 0 to 4.04 micrograms/(kg.d) in females. Compared with the population in a low HEC incidence area, Suixian county, Henan province, the urinary Sa/So ratio of males in the endemic area was statistically significant higher, although no difference was observed in females. The results indicated that fumonisin might be one of the risk factors for the occurrence of HEC.

Topics: Adult; Edible Grain; Esophageal Neoplasms; Female; Food Contamination; Fumonisins; Fusarium; Humans; Male; Mycotoxins; Sphingosine

We surveyed households in rural and urban areas of KwaZulu Natal, South Africa, to assess the exposure of the inhabitants to fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium verticillioides. In southern African regions maize, used as a staple food by the population, is prone to F. verticillioides infection. Furthermore, high levels of FB(1) in maize have been associated with esophageal cancer in South Africa. We assessed exposure of the population to FB(1) at three levels, namely, by analyzing stored maize, plate-ready food, and feces. The positions of participating households in the rural area were recorded using geographic information systems (GIS) for ease and accuracy of follow-up. Of the 50 rural maize samples examined, 32% had levels of FB(1) ranging from 0.1-22.2 mg/kg, whereas 29% of the 28 cooked maize (phutu) samples contained FB(1) ranging from 0.1-0.4 mg/kg. The incidence and levels of FB(1) in feces were 33% and 0.5-39.0 mg/kg, respectively. Of the 49 urban maize samples analyzed 6.1% had a range of 0.2-0.5 mg/kg FB(1), whereas 3 of 44 fecal samples (6%) ranged between 0.6 and 16.2 mg/kg. No FB(1) was detected in urban phutu samples. Because these levels are lower than those published from regions in South Africa with high incidence of esophageal cancer, it may be concluded that the risk of esophageal cancer from FB(1) exposure is lower in the KwaZulu Natal region.

Topics: Carboxylic Acids; Chromatography, High Pressure Liquid; Environmental Exposure; Esophageal Neoplasms; Feces; Food Contamination; Fumonisins; Humans; Incidence; Mycotoxins; Rural Health; South Africa; Urban Health; Zea mays

This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.

Topics: Animals; Carboxylic Acids; Disease Outbreaks; Encephalomalacia; Esophageal Neoplasms; Female; Fumonisins; Fusarium; History, 20th Century; Humans; Male; Mycoses; Mycotoxins; Pulmonary Edema; South Africa; Zea mays

Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence.. Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up: 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline.. No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/ sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use. and alcohol use.. Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC.

Topics: Adult; Aged; Biomarkers; Carboxylic Acids; Carcinogens, Environmental; Carcinoma, Squamous Cell; Case-Control Studies; China; Chromatography, High Pressure Liquid; Environmental Exposure; Esophageal Neoplasms; Female; Food Contamination; Fumonisins; Humans; Male; Middle Aged; Mycotoxins; Risk Assessment; Sphingolipids; Sphingosine; Zea mays

In a previous study, we showed that, of a group of lipids including arachidonic acid (AA), prostaglandins E2 (PGE2) and A2 (PGA2), PGA2 had the most marked effect on the inhibition of cell growth, activation of tyrosine kinase activity, lowering of the number of G1-phase cells, and induction of p53 levels in oesophageal carcinoma (WHCO3) cells. No significant effects by the three lipids were seen in normal monkey kidney cells. In the present study, the effects of the inhibitor of ceramide synthesis, fumonisin B1 (FB1), a metabolite of Fusarium verticillioides (= F. moniliforme) which is implicated in the high incidence of oesophageal cancer, were determined on AA, PGE2 and PGA2 WHCO3 treated cells. In the presence of FB1, the lipid-enhanced tyrosine kinase activity was lowered. Flow cytometric and morphological studies showed that FB1 lowered the marked apoptosis induced by especially PGA2. FB1, however, in combination with AA, PGE2 or PGA2 increased the number of G2/M cells. AA>PGE2>PGA2 alone decreased CDC2-kinase activity, but, in the presence of FB1, CDC2-kinase activity was significantly increased. The PGA2- and AA-induced p53 levels were lowered in the presence of FB1. We concluded that FB1 diminished the cytotoxic effects of the lipids on oesophageal tumour cells.

Topics: Animals; Apoptosis; Arachidonic Acid; Carboxylic Acids; Carcinogens, Environmental; Carcinoma, Squamous Cell; CDC2 Protein Kinase; Cell Cycle; Cell Division; Dinoprostone; Esophageal Neoplasms; Fumonisins; Humans; Prostaglandins; Protein Kinases; Protein-Tyrosine Kinases; Tumor Cells, Cultured; Tumor Suppressor Protein p53

Fusarium moniliforme is the primary fungus contaminating corn throughout the world. Fumonisin B1 (FB1) is the major metabolite of F. moniliforme. It has been shown that FB1 is the promoter and initiator of liver cancer in rat. The corn of Cixian, in Hebei Province, the high-risk area for esophageal cancer in China, is often contaminated by this fungus. A total of 21 corn samples were collected from households in the Cixian County. High levels of FB1 (88.90+/-13.1 microg/g) were found in 10 moldy samples, and low levels (1.40+/-0.50 microg/g) of FB1 were found in 11 apparently healthy corn samples. The positive detection rates of FB1 in moldy and normal samples were 100 and 90.9%, respectively. The frequency of FB1 contamination in the high-risk area is about twice that in the low-risk areas, and the average content of FB1 in samples from high-risk areas was approximately three times that from low-risk areas. Our data indicate that FB1-contaminated corn may be involved in the carcinogenesis of esophageal cancer in high-risk areas of North China.

Topics: Carboxylic Acids; China; Esophageal Neoplasms; Fumonisins; Humans; Risk Factors; Teratogens; Zea mays

Fumonisins and N-nitrosamines (NNO) are suggested risk factors in the development of human oesophageal cancer; exposure to both occurs in high risk populations in Africa and People's Republic of China. The hypothesis that the two would interact in oesophageal carcinogenesis was therefore tested by treating male rats with the known oesophageal carcinogen N-methylbenzylnitrosamine (NMBA), and fumonisin B1 (FB1). The treatment groups were: Group 1, NMBA (2.5 mg/kg) intraperitoneally twice per week from week 2 to 4 inclusive; Group 2, as for group 1 but in addition FB1 (5 mg/kg) daily from weeks 1 to 5 inclusive by gavage; Group 3, FB1 (5 mg/kg) alone daily from weeks 1 to 5 inclusive by gavage, and Group 4, vehicle treatment from week 1 to 5 inclusive. Two of 12 animals in group 1 developed oesophageal papillomas and a further two had oesophageal dysplasia. Data were similar in group 2, animals receiving both NMBA and FB1, with one of 12 animals having papillomas and three of 12 with dysplasia. Sphingolipid biosynthesis was affected in the kidney and slightly in the liver after fumonisin treatment but not in the oesophagus or lung as determined by sphinganine:sphingosine ratios in urine and tissues. These data show that there is no synergistic interaction between NMBA and FB1 in the rat oesophagus when the two compounds are administered together. It is nevertheless important to examine other experimental models and treatment protocols which may be more relevant to the human situation and also to pursue epidemiological investigations of the role of fumonisins in oesophageal cancer.

Topics: Animals; Carboxylic Acids; Carcinogens; Cocarcinogenesis; Dimethylnitrosamine; Drug Synergism; Esophageal Neoplasms; Fumonisins; Infusions, Parenteral; Male; Papilloma; Rats

Forty-seven corn samples were collected in 1989 from Linxian and Shangqiu Counties in Henan Province, the high- and low-risk areas, respectively, for human esophageal cancer in the People's Republic of China. The samples were analyzed for fumonisin (fumonisin B1 [FB1] and FB2) contamination. Of the fumonisin-positive samples, the mean levels in Linxian corn were found to be 872 ng/g for FB1 and 448 ng/g for FB2, while the Shangqiu corns had 890 ng of FB1 and 330 ng of FB2 per g. The incidence of fumonisin contamination of Linxian corn (48%) was about two times higher than that of Shangqiu corn (25%), and the former corn samples were frequently cocontaminated with trichothecenes. Fusarium species isolated from corn from Linxian County produced FB1 at levels ranging from 1,280 to 11,300 micrograms/g.

Topics: Carcinogens, Environmental; China; Esophageal Neoplasms; Fumonisins; Fusarium; Humans; Mycotoxins; Risk Factors; Zea mays

Consumption of grains contaminated with Fusarium moniliforme (Sheldon) causes liver cancer in rats and has been correlated with esophageal cancer in humans. The causative agents are believed to be a family of compounds known as fumonisins, which bear remarkable structural resemblances to sphingosine and sphinganine, the long-chain (sphingoid) base backbones of sphingolipids. Recently, fumonisin B1 has been shown to block de novo synthesis of sphingolipids by inhibiting sphingosine (sphinganine) N-acyltransferase, which leads to accumulation of sphingoid bases. Because the exogenous addition of sphingosine and sphingosine 1-phosphate to Swiss 3T3 cells has been shown to stimulate DNA synthesis (Zhang, H., Buckley, N.E., Gibson, K., and Spiegel, S. (1990) J. Biol. Chem. 265, 76-81; Zhang, H., Desai, N.N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167), we hypothesized that fumonisins might stimulate DNA synthesis by disrupting sphingolipid metabolism. Fumonisin B1 caused accumulation of sphinganine and sphingosine in Swiss 3T3 fibroblasts and, as occurred when these sphingoid bases were added exogenously, stimulated thymidine incorporation into DNA and augmented the mitogenic effect of insulin in a concentration-dependent manner. The mechanism underlying the mitogenic effect of fumonisin B1 was further investigated by using beta-fluoroalanine to block the initial step of sphingolipid biosynthesis catalyzed by serine palmitoyltransferase. beta-Fluoroalanine reduced sphingoid base accumulation in fumonisin B1-treated fibroblasts and inhibited fumonisin B1-stimulated DNA synthesis, but had no effect on mitogenesis when added alone. Fumonisin B1 did not cause accumulation of sphinganine 1-phosphate; therefore, it appears that sphingoid bases per se can stimulate DNA synthesis. To prove that the 1-phosphate is not obligatory, a 1-deoxysphinganine was synthesized, and it was as potent as sphinganine in stimulating DNA synthesis. These results establish that fumonisin B1 is mitogenic via accumulation of sphingoid bases rather than inhibition of complex sphingolipid biosynthesis per se. Because mitogens can often affect cell transformation, this provides a plausible molecular mechanism to explain the carcinogenicity of fumonisins.

Topics: 3T3 Cells; Animals; Carcinogens, Environmental; DNA; DNA Replication; Dose-Response Relationship, Drug; Esophageal Neoplasms; Fumonisins; Fusarium; Humans; Kinetics; Liver Neoplasms; Mice; Models, Biological; Mycotoxins; Rats; Sphingolipids; Sphingosine; Time Factors

A total of 31 corn samples collected from households in the counties of Cixian and Linxian of the People's Republic of China, where high incidences of esophageal cancer have been reported, were analyzed for fumonisin B1 (FB1), aflatoxin, and total trichothecene mycotoxins. High levels of FB1 (18 to 155 ppm; mean, 74 ppm) were found in 16 of the samples that showed heavy mold contamination. FB1, at lower levels (20 to 60 ppm; mean, 35.3 ppm), was also found in 15 samples, collected from the same households, that did not show any visible mold contamination. The levels of aflatoxin in the samples were low (1 to 38.4 ppb; mean, 8.61 ppb). High levels of total type-A trichothecenes were also found in the moldy corn samples (139 to 2,030 ppb; mean, 627 ppb). Immunochromatography of selected samples revealed that these samples contained T-2 toxin, HT-2 toxin, iso-neosolaniol, monoacetoxyscirpenol, and several other type-A trichothecenes. The concentration of total type-B trichothecenes in 15 moldy corn samples was in the range of 470 to 5,826 ppb (mean, 2,359 ppb). High levels (3.7 to 5.0 mg/g) of FB1 were produced in corn in the laboratory by five Fusarium moniliforme strains isolated from the moldy corn. These fungi were also capable of forming various nitrosamines (5 to 16 micrograms per flask) in the presence of nitrate and precursor amines.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: China; Esophageal Neoplasms; Food Contamination; Fumonisins; Fusarium; Incidence; Mycotoxins; Nitrosamines; Zea mays

A semi-purified corn-based diet containing 50 mg/kg of pure (not less than 90%) fumonisin B1 (FB1), isolated from culture material of Fusarium moniliforme strain MRC 826, was fed to a group of 25 rats over a period of 26 months. A control group of 25 rats received the same diet without FB1. Five rats from each group were killed at 6, 12, 20 and 26 months. The liver was the main target organ in the FB1-treated rats and the hepatic pathological changes were identical to those previously reported in rats fed culture material of F.moniliforme MRC 826. All FB1-treated rats that died or were killed from 18 months onwards suffered from a micro- and macronodular cirrhosis and had large expansile nodules of cholangiofibrosis at the hilus of the liver. Ten out of 15 FB1-treated rats (66%) that were killed and/or died between 18 and 26 months developed primary hepatocellular carcinoma. Metastases to the heart, lungs or kidneys were present in four of the rats with hepatocellular carcinoma. No neoplastic changes were observed in any of the control rats. Chronic interstitial nephritis was present in the kidneys of FB1-treated rats killed after 26 months. No lesions were observed in the esophagus, heart or forestomach of FB1-treated rats and this is contrary to previous findings when culture material of the fungus was fed to rats. It is concluded that FB1 is responsible for the hepatocarcinogenic and the hepatotoxic but not all the other toxic effects of culture material of F.moniliforme MRC 826 in rats.

Topics: Adenoma, Bile Duct; Animals; Carcinogens, Environmental; Esophageal Neoplasms; Food Microbiology; Fumonisins; Kidney; Liver; Liver Cirrhosis, Experimental; Liver Neoplasms, Experimental; Male; Mycotoxins; Precancerous Conditions; Rats; Rats, Inbred Strains