Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays

Gelderblom, Wentzel C. A.; Cawood, M.E.; Snyman, S.D.; Vleggaar, Robert; Marasas, Walter F. O.

doi:10.1016/0278-6915(93)90155-r

Cited by 151 publications

(125 citation statements)

References 17 publications

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“…Gelderblom and coworkers in South Africa (11) demonstrated that pure FB 1 can cause an increased incidence of hepatocellular carcinoma when fed to rats for 2 years at 50 µg/g feed. Subsequent studies demonstrated hepatocarcinogenesis of FB 1 , FB 2 , and FB 3 in short-term (3 week) initiationpromotion bioassays in the rat (9). Fumonisins are also acutely hepatotoxic, and it has been proposed that liver cell necrosis and regeneration play a role in carcinogenicity of fumonisins (9).…”

Section: Toxicity and Carcinogenicity In Experimental Animal Systemsmentioning

confidence: 99%

Fumonisins in Maize: Can We Reduce Their Occurrence?

1997

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Section: Toxicity and Carcinogenicity In Experimental Animal Systemsmentioning

confidence: 99%

Fumonisins in Maize: Can We Reduce Their Occurrence?

1997

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“…The primary amine group of FB 1 has been suggested as the site of toxicity for the molecule (17,18). Detoxification of FB 1 by blocking the amine group with a reducing sugar such as fructose or glucose via the nonenzymatic browning (NEB) or Maillard reaction has been suggested (19).…”

Section: Introductionmentioning

confidence: 99%

Glucose Reaction with Fumonisin B₁Partially Reduces Its Toxicity in Swine

Fernandez-Surumay

Osweiler

Yaeger

et al. 2004

J. Agric. Food Chem.

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Acute and subacute intraperitoneal doses of fumonisin B1 (FB1) were administered to test the efficacy of the FB1-glucose reaction products in detoxifying FB1 in swine. In the acute study at 11 µmol of FB1/kg of body weight, five of six pigs administered FB1 and four of six pigs administered FB1-glucose died from acute pulmonary edema. Analysis of weight gain, serum aspartate aminotransferase and γ-glutamyltransferase, total cholesterol, and pathological evaluation did not provide evidence of protection against FB1 toxicity by the FB1-glucose reaction products. In the subacute study at 5.5 µmol of FB1/kg of body weight, one pig administered FB1 died from liver damage. Analysis of serum aspartate aminotransferase, γ-glutamyltransferase, and total bilirubin showed protection against FB1 toxicity by the FB1-glucose reaction products. The levels of sphinganine and sphinganine/sphingosine ratios in serum and liver as well as pathologic findings provided definitive evidence of protection against the FB1 toxic effects by this detoxification procedure (p < 0.05). Acute and subacute intraperitoneal doses of fumonisin B 1 (FB 1 ) were administered to test the efficacy of the FB 1 -glucose reaction products in detoxifying FB 1 in swine. In the acute study at 11 µmol of FB 1 /kg of body weight, five of six pigs administered FB 1 and four of six pigs administered FB 1 -glucose died from acute pulmonary edema. Analysis of weight gain, serum aspartate aminotransferase and γ-glutamyltransferase, total cholesterol, and pathological evaluation did not provide evidence of protection against FB 1 toxicity by the FB 1 -glucose reaction products. In the subacute study at 5.5 µmol of FB 1 /kg of body weight, one pig administered FB 1 died from liver damage. Analysis of serum aspartate aminotransferase, γ-glutamyltransferase, and total bilirubin showed protection against FB 1 toxicity by the FB 1 -glucose reaction products. The levels of sphinganine and sphinganine/sphingosine ratios in serum and liver as well as pathologic findings provided definitive evidence of protection against the FB 1 toxic effects by this detoxification procedure (p < 0.05).

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“…Fumonisins induced both GGT and the placental form of glutathione S-transferase (GSTP)-positive foci in BD IX and Fischer rats (5,62,70,71). Foci induction in diethylnitrosamine-pretreated Fischer rats was dose related, and GSTP was a more sensitive marker than GGT ( Figure 3) (70).…”

Section: Hepatotoxicitymentioning

confidence: 98%

“…Conversely, the link between F. moniliforme and fumonisin has been independently established by several research groups; that is, the in vivo toxicities of corn (involved in ELEM outbreaks) naturally contaminated with F. moniliforme (9,55), culture materials of (toxic) F. moniliforme isolates, polar culture material extracts, and purified FB 1 are qualitatively the same (5,32,45,(56)(57)(58)(59)(60)(61). FB 2 , fumonisin B 3 (FB 3 ), and probably also hydrolyzed FB 1 (HFB 1 ) exert the same in vivo effects (62)(63)(64).…”

Section: Toxicology: Subchronic Effects Of Fumonisins In Ratsmentioning

confidence: 99%

“…A study by Hendrich et al (63) showed that nixtamalization did not reduce hepatotoxicity or cancer-promoting activity of F. proliferatum culture material, even though FB 1 and FB 2 were converted to HFB 1 and HFB 2 . However, others reported that although cytotoxic in vitro, purified HFB 1 had no effect in vivo, and they proposed that it was not gastrointestinally absorbed (62). To further study nixtamalization and in vivo toxicity, Voss (92) fed rats F. moniliforme culture material providing 71 ppm FB 1 , water-extracted culture material providing about 11 ppm FB 1 , or a nixtamalized culture material providing 58 ppm HFB 1 , but no measurable FB 1 .…”

Section: Reproduction and Teratology Studiesmentioning

confidence: 99%

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An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

Voss

Riley

Norred

et al. 2001

Environ Health Perspect

120

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Fumonisins are produced by Fusarium moniliforme F. verticillioides) and other Fusarium that grow on corn worldwide. They cause fatal toxicoses of horses and swine. Their effects in humans are unclear, but epidemiologic evidence suggests that consumption of fumonisin-contaminated corn contributes to human esophageal cancer in southern Africa and China. Much has been learned from rodent studies about fumonisin B1(FB1), the most common homologue. FB1 is poorly absorbed and rapidly eliminated in feces. Minor amounts are retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause the same liver cancer promotion and subchronic (studies (3/4) 90 days) liver and kidney effects as (italic)F. moniliforme. FB 1 induces apoptosis of hepatocytes and of proximal tubule epithelial cells. More advanced lesions in both organs are characterized by simultaneous cell loss (apoptosis and necrosis) and proliferation (mitosis). Microscopic and other findings suggest that an imbalance between cell loss and replacement develops, a condition favorable for carcinogenesis. On the molecular level, fumonisins inhibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretically, sphingolipid-mediated regulatory processes that influence apoptosis and mitosis. Liver sphingolipid effects and toxicity are correlated, and ceramide synthase inhibition occurs in liver and kidney at doses below their respective no-observed-effect levels. FB1 does not cross the placenta and is not teratogenic in vivoin rats, mice, or rabbits, but is embryotoxic at high, maternally toxic doses. These data have contributed to preliminary risk evaluation and to protocol development for carcinogenicity and chronic toxicity studies of FB1 in rats and mice.

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Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays

Cited by 151 publications

References 17 publications

Fumonisins in Maize: Can We Reduce Their Occurrence?

Fumonisins in Maize: Can We Reduce Their Occurrence?

Glucose Reaction with Fumonisin B₁Partially Reduces Its Toxicity in Swine

An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

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Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays

Cited by 151 publications

References 17 publications

Fumonisins in Maize: Can We Reduce Their Occurrence?

Fumonisins in Maize: Can We Reduce Their Occurrence?

Glucose Reaction with Fumonisin B1Partially Reduces Its Toxicity in Swine

An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

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Product

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Glucose Reaction with Fumonisin B₁Partially Reduces Its Toxicity in Swine