Fumonisin B<sub>1</sub> dosimetry in relation to cancer initiation in rat liver

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

doi:10.1093/carcin/15.4.790

Cited by 37 publications

(20 citation statements)

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“…However, FB 1 induces oxidative damage [23] and exhibited clastogenic properties [24], suggesting that the compound could either directly or indirectly, induce DNA damage. Short-term studies utilizing a cancer initiating/promoting model in rat liver indicated that FB 1 closely mimics the characteristics of other genotoxic carcinogens with respect to initiation [18]. With respect to cancer promotion, evidence supports a hypothesis that FB 1 effects a growth differential, during which initiated hepatocytes proliferate in an environment where the growth of normal cells is inhibited [25].…”

Section: Introductionmentioning

confidence: 61%

“…With respect to cancer promotion, evidence supports a hypothesis that FB 1 effects a growth differential, during which initiated hepatocytes proliferate in an environment where the growth of normal cells is inhibited [25]. This became evident as FB 1 inhibits the epidermal growth factor (EGF) stimulatory response in primary hepatocytes in vitro [26] and hepatocyte regeneration following partial hepatectomy in vivo [18] suggesting that FB 1 induces a growth differential similar to most cancer promoters [27,28].…”

Section: Introductionmentioning

confidence: 65%

“…Male Fischer rats (150 g body weight) were fed a modified AIN-76 diet after weaning [18] and housed individually in a controlled environment (23-25°C) with a 12 h light/dark cycle with free access to feed and drinking water. FB 1 was dissolved in methanol prior to application on a subsample (200 g) of the AIN-76A diet and dried overnight.…”

Section: Animals and Dietsmentioning

confidence: 99%

“…FB 1 causes several diseases in animals and is associated with a high incidence of human oesophageal and liver cancer in certain geographical areas in the world [13,14], and the development of neural tube defects [15]. FB 1 is hepatotoxic and hepatocarcinogenic [16,17] when chronically fed to rats and effects both cancer initiation and promotion properties in a short-term rat liver carcinogenesis model [18,19]. This model provides an excellent opportunity to study the mechanisms associated with cancer induction by this ''apparent'' nongenotoxic compound as it lacks genotoxicity in the Salmonella mutagen and DNA repair assays [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Burger

Abel

Snijman

et al. 2007

Lipids

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Alteration of lipid constituents of cellular membranes has been proposed as a possible mechanism for cancer promotion by fumonisin B(1 )(FB(1)). To further investigate this hypothesis a dietary dosage which initiates and promotes liver cancer (250 mg FB(1)/kg) was fed to male Fischer rats for 21 days and the lipid composition of plasma, microsomal, mitochondrial and nuclear subcellular fractions determined. The effect of FB(1) on the cholesterol, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), as well as sphingomyelin (SM) and the phospholipids-associated fatty acid (FA) profiles, were unique for each subcellular membrane fraction. PE was significantly increased in the microsomal, mitochondrial and plasma membrane fractions, whereas cholesterol was increased in both the microsomal and nuclear fraction. In addition SM was decreased and increased in the mitochondrial and nuclear fractions, respectively. The decreased PC/PE and polyunsaturated/saturated (P/S) FA ratio in the different membrane fractions suggest a more rigid membrane structure. The decreased levels in polyunsaturated fatty acids in PC together with a pronounced increase in C18:1omega9 and C18:2omega6 were indicative of an impaired delta-6 desaturase. The increased omega6/omega3 ratio and decreased C20:4omega6 PC/PE ratio due to an increase in C20:4omega6 in PE relatively to PC in the different subcellular fractions suggests a shift towards prostanoid synthesis of the E2 series. Changes in the PE and C20:4omega6 parameters in the plasma membrane could alter key growth regulatory and/or other cell receptors in lipid rafts known to be altered by FB(1). An interactive role between C20:4omega6 and ceramide in the mitochondria, is suggested to regulate the balance between proliferation and apoptosis in altered initiated hepatocytes resulting in their selective outgrowth during cancer promotion effected by FB(1).

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Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 65%

Section: Animals and Dietsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Burger

Abel

Snijman

et al. 2007

Lipids

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“…In addition to yield losses, F. verticillioides infection of maize ears results in contamination with fumonisin mycotoxins. Fumonisins cause the animal diseases equine leukoencephalomalacia (Marasas et al 1988) and porcine pulmonary edema (Colvin and Harrison 1992), are known to cause liver cancer in laboratory animals (Gelderblom et al 1994), and are associated with esophageal cancer (Yoshizawa et al 1994) and neural tube defects in humans (Hendricks 1999). In 2010, the genome sequence of F. verticillioides strain M-3125 was published providing a strong foundation for studying F. verticillioides biology (Ma et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Mating type and spore killing characterization of Fusarium verticillioides strains

et al. 2015

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Fusarium verticillioides is a heterothallic ascomycete causing maize ear rot, and produces fumonisin mycotoxins harmful to livestock and human health. A meiotic drive phenomenon called spore killing has been reported in several filamentous fungi including F. verticillioides. F. verticillioides reference genome strain M-3125 (FGSC 7600) is spore killer sensitive (SK S ), and genetic crosses of M-3125 with a strain carrying SK K (the killer element) result in only four viable ascospores per ascus instead of the normal eight ascospores. We sought to identify a strain of F. verticillioides that is SK S and MAT1-2 for use in genetic analysis with M-3125. To accomplish this, we screened 50 F. verticillioides strains from the Fusarium Research Center at The Pennsylvania State University, USA for spore killing. To characterize the mating types of these strains, portions of the MAT locus idiomorphs were amplified using polymerase chain reaction, and genetic crosses were performed. The PCR amplification results show that 18 of the 50 strains are MAT1-2 and 32 are MAT1-1. Genetic crosses between M-3125 and 11 of the 18 MAT1-2 strains produced normal perithecia. Crosses between two (M-8024 and M-7815) of the 11 strains and M-3125 produced perithecia with eight ascospores per ascus, and nine others had only four ascospores per ascus, suggesting that M-8024 and M-7815 are SK S and the other nine are SK K . This study expands our knowledge of mating type and spore killing in F. verticillioides and identifies two SK S , MAT1-2 strains for use in genetic crosses with genome reference strain M-3125.

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Intravenous fumonisin B₁ induces cell proliferation and apoptosis in the rat

Lim¹,

Parker²,

Vesonder

et al. 1996

Natural Toxins

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In the rat, the target organs of fumonisin B1, a mycotoxin produced by Fusarium moniliforme, are the kidney and liver. Fumonisin B1 is also hepatocarcinogenic in the rat and is associated epidemiologically with esophageal cancer in humans. We investigated the effect of a single intravenous dose of fumonisin B1 on cell proliferation, lesion development, and glutathione status in the major target organs of the rat. Male Sprague-Dawley rats were injected intravenously with fumonisin B1 at 0 or 1.25 mg/kg and were euthanized at 12 hr or, 1,2,3, or 5 days. An intraperitoneal injection of 5-bromo-2'-deoxyuridine at 100 mg/kg was given 90 min prior to euthanasia. In fumonisin B1 treated rats, serum cholesterol and serum urea nitrogen were elevated; however, the activity of hepatic enzymes was unaffected. Hepatic and renal glutathione concentrations were depressed at 12 and 24 hr, respectively, with subsequent recovery. Histologic changes were most prominent in the outer medulla of the kidney, with cell proliferation and apoptosis followed by nephrosis. Cell proliferation also occurred in the liver and esophagus, but in the absence of tissue injury. The labeling index peaked on day 1 for the liver and on day 3 for the esophagus. These results confirm that the primary target organ of fumonisin B1 in the rat is the kidney and support the concept that fumonisin B1-induced mitogenesis may be the mechanism of carcinogenesis.

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Fumonisin B₁ dosimetry in relation to cancer initiation in rat liver

Cited by 37 publications

References 0 publications

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Mating type and spore killing characterization of Fusarium verticillioides strains

Intravenous fumonisin B₁ induces cell proliferation and apoptosis in the rat

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Fumonisin B1 dosimetry in relation to cancer initiation in rat liver

Cited by 37 publications

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Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B1

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B1

Mating type and spore killing characterization of Fusarium verticillioides strains

Intravenous fumonisin B1 induces cell proliferation and apoptosis in the rat

Contact Info

Product

Resources

About

Fumonisin B₁ dosimetry in relation to cancer initiation in rat liver

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Intravenous fumonisin B₁ induces cell proliferation and apoptosis in the rat