T-2-Toxin

The Tri3 gene of F. sporotrichioides encodes a 15-O-acetyl-trans-ferase that acetylates the 15-OH of 15-deacetylcalonectrin (117) (292). This enzyme also acetylates the 3o -hydroxyl in a number of 12,13-epoxytrichothecene substrates. The C-15 acetylation step appears to be essential to the pathway to T-2 toxin and Tri3 mutants accumulate neither T-2 toxin nor the major co-metabolites 4,15-diacetoxyscirpenol (121) and neosolaniol (128). 

15-Diacetoxyscirpenol (121), neosolaniol (128) and T-2 toxin (103) result from deacetylation of their respective 3-acetyl derivatives. 

An esterase with higher affinity for the ester bond at the 3a position than at the 4/3 position and with some specificity for 3-acetylT-2 toxin has been partially purified and characterised from F. sporotrichioides (296). 

The isovalerate moiety present in T-2 toxin is derived by decar-boxylative transamination from L-leucine (297, 298). Leucine limitation enhances the production of neosolaniol (128). 

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Toxins (typically high molecular weight proteins), such as botulinum toxin, ricin, or Staphyloccocal enterotoxin (SEB) or T-2 toxin (which actually is a small molecule). 

Of four basic trichothecene groups (A, B, C and D), types A and B represent the most important mycotoxins. Type A includes the T-2 toxin that can suppress the immune system and can cause damage to bone marrow. The T-2 toxin is about 14 times more toxic than the most widespread Fusarium-based type B mycotoxin, deoxynivalenol (DON), previously called vomitoxin. DON is a... 

Deoxynivalenol Nivalenol Zearalenone T-2 toxin Moniliformin Ochratoxin A Aflatoxins... 

Ramakrishna N, Lacey J and Smith J E (1996b), The effects of fungal competition on colonization of barley grain by Fusarium sporotrichioides on T-2 toxin formation . Food Addit. Contam., 13, 939-948. 

Rizzo A F, Atroshi F, Ahotupa M, Sankari S and Elovaara E (1994), Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin , Zentralb. Veterinarmed. A, 41 (2), 81-90. 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

Ueno, Y. Toxicological features of T-2 toxin and related trichothecenes. Fundam. Appl. Toxicol. 4, S124, 1984. 

Samara, A. et al. Induction of differentiation in human myeloid leukemic cells by T-2 toxin and other trichothecenes. Toxicol. Appl. Pharmacol. 89, 418, 1987. 

Islam, Z. et al. Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice. Biosci. Biotechnol. Biochem. 62, 1492, 1998. 

Middlebrook, J. L. and Leatherman D.L. Binding of T-2 toxin to eukaryotic cell ribosomes, Biochem. Pharmacol. 38, 3103, 1989. 

Witt, M. F. and Pestka J.J. Uptake of the naturally occurring 3-alpha-hydroxy isomer of T-2 toxin by a murine B cell hybridoma. Food Chem. Toxicol. 28, 21, 1990. 

Ueno, Y. et al. Induction of apoptosis by T-2 toxin and other natural toxins in HL-60 human promyelotic leukemia cells. Nat. Toxins. 3, 129, 1995. 

Shinozuka, J. etal. T-2 toxin-induced apoptosis in lymphoid organs of mice. Exp. Toxicol. Pathol. 49, 387, 1997. 

Taylor, M. J. et al. Increased endotoxin sensitivity following T-2 toxin treatment is associated with increased absorption of endotoxin. Toxicol. Appl. Pharmacol. 109, 51, 1991. 

Jemmali M, Ueno Y, Ishii K, Frayssinet C, Etienne M (1978) Natural occurrence of trichothecenes, nivalenol, deoxynivalenol, T-2 toxin and zearalenone in corn. Experientia 34 1333-1334 Josephs RD, Schuhmacher R, Krska R (2001) International interlaboratory study for the determination of the Fusarium mycotoxins zearalenone and deoxynivalenol in agricultural commodities. Food Addit Contam 18 417-430... 

Caution The T-2 mycotoxins are the only potential biological warfare agents that can harm and be absorbed through intact skin. Aerosol doses of T-2 toxins may be ten times more potent than parenteral doses. 

A number of fusarium mycotoxins are produced, depending upon geographic origin. Among them are deoxynivalenol, zearalenone, fumonisins, and T-2 toxin. 

Figure 9.3 Chemical structures of (a) thichothecenes (including deoxynivalenol and T-2 toxin), (b) zearalenone, and (c) fumonisin BL...

Deoxynivalenol and T-2 toxin levels may be reduced in pasta during boiling as toxins are passed into the cooking water (Scott, 1991). In tortilla production, only 18 to 28% of trichothecene content remained after boiling in a calcium hydroxide solution as part of the tortilla-making process (Abbas et al., 1988). Trichothecenes are unstable in the presence of alkali. 

Swanson, S.P. et ah. Metabolism of three trichothecene mycotoxins, T-2 toxin, diacetoxyscirpenol and deox5mivalenol, by bovine rumen microorganisms, J. Chromatogr., 414, 335, 1987. 

Torp, M., and Langseth, W. (1999). Production of T-2 toxin by a Fusarium resembling Fusarium poae. Mycopathologia 147, 89-96. 

Burmeister HR (1971) T-2 toxin production by Fusarium tricinctum on sohd substrate. Appl Microbiol 21 739-742... 

Bunner DL, Upshall DG, Bhatti AR (1985) Toxicology data on T-2 toxin. In Report of focus officers meeting on mycotoxin toxicity, Defense research establishment at Suffield Alta, Canada, 23-24 Sept 1985... 

T-2 Toxin see Toxins derived from Fusarium sporotrichioides)... 

T-2 Toxin (see Toxins derived from Fusarium sporolrichioides) Toxins derived from Fusarium graminearum, F. culmorum and... 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

A point of potential misidentification should be mentioned here. 2C-T-2 has occasionally been called, simply, T-2. This abbreviated nickname has also been used for T-2 Toxin, a mycotoxin of the Tricothecene group, formed mainly by the Fusarium spp. This is the infamous warfare agent in Southeast Asia, which was finally identified as bee feces rather than a Soviet military adventure. T-2 and 2C-T-2 are radically different compounds. 

Joint FAO/WHO Expert Committee on Food Additives (JECFA), 2001. Safety evaluation of certain mycotoxins in food. Deoxynivalenol, HT-2 and T-2 toxin. FAO Food and Nutrition Paper 74. http //www.inchem.org/ documents/jecfa/jecmono/v4 7je01.htm... 

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