fumonisin-b1 and Neoplasms

Topics: Animals; Carcinogens, Environmental; Food Contamination; Fumonisins; Humans; Mycotoxins; Neoplasms; Structure-Activity Relationship; Zea mays

The history, toxicological effects, world-wide natural occurrence and impact of the fumonisins, food-borne carcinogenic mycotoxins produced by Fusarium moniliforme, are reviewed from the original description of the fungus in 1881 to the present. Following the isolation and characterization of fumonisin B1 and B2 and the publication of the first 3 papers on fumonisins by South African researchers in 1988, the interest in these compounds increased dramatically during 1989 and 1990 because of numerous outbreaks of mycotoxicoses in animals associated with the 1989 corn crop in the USA. Major advances made during this period were published in approximately 49 papers from 1988 to 1991. During the period 1992 to 1994, there was an explosion in the literature on fumonisins and at least 212 papers were published. The information contained in the more than 260 papers on fumonisins published to date is reviewed with respect to toxicological effects, association with animal and human diseases, and world-wide natural occurrence in corn and corn-based feeds and foods. Impact of the fumonisins is addressed with respect to their implications for human and animal health, risk assessment and establishment of tolerance levels.

Topics: Animals; Carcinogens, Environmental; Fumonisins; History, 19th Century; History, 20th Century; Humans; Mycotoxins; Neoplasms; Zea mays

The presence of fumonisins and associated mycotoxins from Fusarium moniliforme in corn-based foods has recently become a concern in North America and elsewhere. Monitoring of various corn based foods and food commodities for fumonisins is ongoing in both the USA and Canada, and the results can be used for preliminary exposure assessments. The role of Fusarium moniliforme and the fumonisins in some diseases of livestock has been established. Considerable information is available on the mechanism of action of the fumonisins. With the availability of increased quantities of pure fumonisins, several subchronic toxicity studies, designed to establish dose response characteristics in rodents have now been completed. However, since concerns about the chronic toxicity of the fumonisins have not yet been adequately addressed, a tolerable daily intake cannot be established at this time. With the information at hand it is, nevertheless, possible to arrive at an interim risk assessment, which can be used to make interim risk management decisions. A total of 361 samples, covering 4 years of a Canadian survey, have been analyzed to date. Of these, 64 contained > or = 0.1 micrograms/g fumonisin B1, and 10 contained > or = 1 microgram/g. The 'all persons' estimate for the intake of fumonisins from these foods was < 0.089 micrograms/kg bw for 5-11 year-old children, and lower for other age groups. Based on an assessment of the available information on the toxicity of fumonisins, it can be concluded that these estimated intakes are unlikely to pose a health risk.

Topics: Animals; Canada; Carcinogens, Environmental; Food Contamination; Fumonisins; Fusarium; Humans; Mycotoxins; Neoplasms; Risk Assessment; Zea mays

Sphingolipids are found in all eukaryotic and some prokaryotic organisms and participate in the regulation of cell growth, differentiation, and diverse cell functions including cell-cell communication, cell-substratum interactions and intracellular signal transduction. Nonetheless, the field of nutrition has given scant attention to these compounds so that little is known about the following fundamental questions: What is the fate of sphingolipids that are consumed in food? Does consumption of dietary sphingolipids affect the behavior of cells in the gastrointestinal tract or other organs? How do other factors in the diet affect sphingolipid metabolism? Several recent findings underscore the importance of these questions, for examples: 1) Sphingolipids are digested throughout the GI tract to ceramide and sphingosine, which are highly bioactive compounds that affect cellular regulatory pathways; 2) addition of sphingomyelin to a standard AIN diet (which is essentially devoid of sphingolipids) reduces the appearance of aberrant colonic crypts, and perhaps the number of tumors, in mice treated with a colon carcinogen; and 3) an enzyme of sphingolipid metabolism has been discovered to be the target of a class of toxic and carcinogenic mycotoxins called fumonisins. Given these recent findings, it is possible that some of the confusion that has arisen regarding the relationships between dietary fat and disease might be due to the lack of consideration of the sphingolipids that are also present.

Topics: Animals; Carcinogens, Environmental; Diet; Digestion; Fumonisins; Humans; Mycotoxins; Neoplasms; Neoplasms, Experimental; Sphingolipids

Sphingolipids have been implicated in apoptosis after various stress inducers. To assess the involvement of the de novo sphingolipid pathway in apoptosis, photodynamic therapy (PDT) with the photosensitizer Pc 4 was used as a novel stress inducer. Here we provide biochemical and genetic evidence of the role of the de novo sphingolipids in apoptosis post-Pc 4-PDT. In Jurkat cells PDT-induced intracellular sphinganine accumulation, DEVDase activation, PARP cleavage, and apoptosis were suppressed by the de novo sphingolipid synthesis inhibitor ISP-1 (Myriocin). Coincubation with sphinganine, sphingosine, or C16-ceramide specifically reversed the antiapoptotic actions of ISP-1 or the singlet oxygen scavenger L-histidine. PDT-induced cytochrome c release from mitochondria into the cytosol was inhibited by L-histidine, but not by ISP-1. Cotreatment with sphinganine did not reverse the inhibitory effect of L-histidine. In addition, PDT-induced sphinganine accumulation and apoptosis were ISP-1-sensitive in A431 human epidermoid and HT29 human carcinoma cells. Furthermore, in LY-B cells, CHO-derived mutants deficient in the de novo sphingolipid synthesis enzyme serine palmitoyltransferase (SPT) activity, DEVDase activation and apoptosis were delayed and suppressed post-PDT. Hence, the data are consistent with the partial involvement of the de novo sphingolipid pathway in apoptosis via DEVDase activation downstream of mitochondrial cytochrome c release post-Pc 4-PDT.

Topics: Acyltransferases; Animals; Apoptosis; Carboxylic Acids; Caspases; CHO Cells; Cricetinae; Cytochrome c Group; Fatty Acids, Monounsaturated; Fumonisins; Histidine; Humans; Indoles; Jurkat Cells; Kinetics; Mitochondria; Models, Chemical; Neoplasms; Photosensitizing Agents; Poly(ADP-ribose) Polymerases; Serine C-Palmitoyltransferase; Sphingolipids; Sphingosine; Tumor Cells, Cultured

Fumonisin B(1) (FB(1)), a carcinogenic mycotoxin produced by the fungus Fusarium verticillioides in corn, causes cancer initiation in rat liver in a similar manner to genotoxic carcinogens although apparently with different kinetics. The present experiment was designed to evaluate the role of regenerative cell proliferation, effected by partial hepatectomy (PH) and carbontetrachloride (CCl(4)) and direct mitogen-induced hyperplasia, induced by lead nitrate (PbNO(3)), on FB(1)-induced cancer initiation. Initiation was effected over a period of 14 days by gavage administration of FB(1) at different daily doses ranging from 0.14 to 3.5 mg FB(1)/100 g body weight while the stimuli for cell proliferation were introduced 7 days after the start of the FB(1) treatment. Based on the proliferative stimulus used, cancer promotion was effected 3 weeks after completion of the initiating treatment by 2-acetylaminofluorene (2-AAF) treatment followed by PH or carbon tetrachloride CCl(4) on day 4. Cancer initiation by FB(1) was associated with a hepatotoxic effect and an increase in lipid peroxidation. In contrast to compensatory liver cell proliferation induced by PH and CCl(4), mitogen-induced hyperplasia (PbNO(3)) failed to enhance the cancer initiating potential of FB(1) suggesting that cancer induction by a non-genotoxic carcinogen is supported by regenerative cell proliferation. Cognizance of the enhancing role of cell proliferation during cancer initiation by FB(1) is required in assessing the risks posed by this mycotoxin to humans.

Topics: 2-Acetylaminofluorene; Animals; Carbon Tetrachloride; Carboxylic Acids; Carcinogens; Cell Division; Dose-Response Relationship, Drug; Fumonisins; Hepatocytes; Lipid Peroxidation; Liver; Male; Neoplasms; Rats; Rats, Inbred F344; Thiobarbituric Acid Reactive Substances; Time Factors

Fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium moniliforme, is a contaminant of cereals with various and complex cellular effects. FB(1) induces liver cancer in rats and has been linked to esophageal cancer in South Africa and China. The mechanisms of FB(1)-induced carcinogenesis are uncertain and the information on FB(1) mutagenic properties is limited and controversial. FB(1) contamination levels in maize and wheat from Chile were found to be similar to those in other countries. FB(1) was devoid of activity in gene mutation assays with Salmonella typhimurium strains TA100, TA102 and TA98. However, i.p. injection of FB(1) induced an increased frequency of micronuclei in mouse bone marrow polychromatic erythrocytes at 25 and 100 mg/kg. We conclude that FB(1) induces in vivo genotoxicity in the absence of in vitro mutagenicity in Salmonella.

Topics: Animals; Bone Marrow Cells; Carboxylic Acids; Dose-Response Relationship, Drug; Fumonisins; Male; Mice; Micronuclei, Chromosome-Defective; Micronucleus Tests; Mutagenicity Tests; Mycotoxins; Neoplasms; Salmonella; Zea mays