Aflatoxin Bi

The keto-carbonyl C signal at 5c = 200.9 would only fit the aflatoxins B, and M,. In the C NMR spectrum an enol ether-C// fragment can also be recognised from the chemical shift value of 5c = 145.8 and the typical one-bond coupling constant Jch = 196 Hz the proton involved appears at Sh = 72, as the CH COSY plot shows. The H triplet which belongs to it overlaps with a sing- 

Partial Proton carbon atom carbon atoms  

Further interpretation of the CH COSY / CH COLOC plots allows additional assignments to be made for fragments B and C of aflatoxin B,. 

Since fragment A was clearly assigned with the help of HH coupling constants, all of the C atoms not included in A, which, according to the CH COLOC plot, are two or three bonds apart from the equivalent protons at Sh = 6.72 (Table 43.1), belong to the benzene ring B. 

Additional evidence for the assignment of the other C atoms is supplied by the CH coupling constants in the Table shown. 

The keto-carbonyl 13C signal at 8C = 200.9 would only fit the aflatoxins B and Mt. In the, 3C NMR spectrum an enol cther-C// fragment can also be recognised from the chemical shift value of 

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An aflatoxin is isolated from Aspergillus flavus. Which of the three aflatoxins, Bi, Gi or Mj, is it given the set of NMR experiments 43 ... 

Palmitic and stearic acids aflatoxins Bi and Bi 15 to 35% unseparated fatty acids intensified the fluorescence when investigating com extracts [224]... 

Liquid paraffin aflatoxin Bi 2.5-fold spray solution, 67% in n-hexane [245]... 

Triton X-100 ethoxyquin (antioxidant in spices) > 200-fold, stabilization > 15 h spray solution, 33% in benzene the fluorescence of aflatoxin Bi is reduced by 10 to 15% [292]. 

Two of the most carcinogenic compounds known dibenzo[a,l]pyrene, a polycyclic aromatic hydrocarbon (PAH) and aflatoxin Bi, a fungal metabolite. 

The normal pathway toward excretion of foreign molecules like aflatoxin Bi and dibenzo [a,/]pyrene, however, also involves nucleophilic substitution reactions of their epoxides. 

Breinholt V, Hendricks J, Pereira C, Arbogast D and Bailey G. 1995. Dietary chlorophyllin is a potent inhibitor of aflatoxin Bi hepatocarcinogenesis in rainbow trout. Cancer Res 55(l) 57-62. 

Trichloroethylene Vinyl chloride CYP3A4 Acetaminophen Aflatoxin Bi and Gi 6-Aminochrysene Benzo[a]pyrene 7,8-dihydrodiol Cyclophosphamide Ifosphamide 1-Nitropyrene Sterigmatocystin Senecionine... 

Dietary Casein Levels and Aflatoxin Bi Metabolism in Rainbow Trout (Salmo gairdneri)... 

Aflatoxin Bi (AFB) is a mold metabolite which has been observed to be acutely toxic and carcinogenic to a wide variety of animals (5,6) and has been implicated in human primary hepatic carcinoma (7, 8). Diets deficient in protein have been reported to increase the susceptibility of mammals to acute AFB toxicity and the induction of cancer (2, 9, 10, 11, 12, 13). Increased dietary proteins have increased the carcinogenic activity of AFB fed to rats (1 4) and trout (15.). Supportive of this latter finding has been the reported direct relationship between dietary protein content and AFB-DNA adduct formation in vivo in rats (16, 17). 

Figure 9.1 Different types of aflatoxins (a) aflatoxin Bi, (b) aflatoxin B2, (c) aflatoxin Gi, (d) aflatoxin G2, (e) aflatoxin Mi.

Denissenko, M.F. et al., Quantitation and mapping of aflatoxin DNA damage in genomic DNA using aflatoxin Bi-8,9-epoxide and microsomal activation systems, Mutat. Res., 425, 205, 1999. 

Riley, J. et al., In vitro activation of the human Harvey-ras proto-oncogene by aflatoxin Bi, Carcinogenesis, 18, 905, 1997. 

It turned out that aflatoxin was actually a mixture of four different but closely related chemicals. All possessed the same molecular backbone of carbon, hydrogen, and oxygen atoms (which backbone was quite complex and not known to be present in any other natural or synthetic chemicals), but differed from one another in some minor details. Two of the aflatoxins emitted a blue fluorescence when they were irradiated with ultraviolet light, and so were named aflatoxin Bi and B2 the names aflatoxin Gi and G2 were assigned to the green-fluorescing compounds. The intense fluorescent properties of the aflatoxins would later prove an invaluable aid to chemists interested in measuring the amount of these substances present in various foods, because the intensity of the fluorescence was related to the amount of chemical present. 

Orotic acid incorporation into nuclear and cytoplasmic RNA is decreased in polycythemic mice [136]. Aflatoxin Bi, a known hepatocarcinogen which induced polysomal disaggregation in the livers of rats, also inhibits the in vivo incorporation of intraperitoneally injected orotic acid into liver RNA [137]. On the other hand, the incorporation of orotic acid into free nucleotides and the RNA of the monkey kidney is rapidly increased twofold after castration and is restored to normal within seven days by the administration of testosterone [134]. It is of interest to note that, in experiments with rats, administration of orotic... 

The aflatoxins are rather unpleasant fungal toxins. At high levels they can cause severe liver damage in animals and humans, and at lower levels they are implicated in liver cancer. These toxins are produced by the fungus Aspergillus flavus, a common contaminant on nuts and grains. Aflatoxin Bi is the most commonly encountered... 

Fortunately, nature provides an alternative nucleophile whose role is to mop up dangerous electrophiles such as aflatoxin Bi epoxide before they can do damage, and to remove them from the body. This compound is glutathione (see Box 6.6), a tripeptide composed of glutamic acid, cysteine, and glycine. 

Halvorson MR, Phillips TD, Safe SH, et al. 1985. Metabolism of aflatoxin BI by rat hepatic microsomes induced by polyhalogenated biphenyl congeners. Appl Environ Microbiol 49(4) 882-886. 

Shepard EC, Phillips TD, Irvin TR. 1984. Aflatoxin BI metabolism in the rat Polyhalogenated biphenyl enhanced conversion to aflatoxin Ml. Xenobiotica 14(9) 741-750. 

The importance of chiral factors in disposition and toxicity has been fully recognized only relatively recently, although important examples have been known for some time. For instance the S(—) enantiomer of thalidomide is known to have greater embryotoxicity than the R(+) enantiomer (see chap. 7). Another example in which a particular isomer of a metabolite is responsible for a carcinogenic effect is the exo-oxide of aflatoxin Bi, discussed later in this chapter (Fig 5.14). 

Both benign and malignant liver tumors may arise from exposure to hepatotoxins and can be derived from various cell types. Thus, adenomas have been associated with the use of contraceptive steroids and exposure to aflatoxin Bi, and dimethylnitrosamine can produce hepatocellular carcinomas, whereas vinyl chloride causes hemangiosarcomas derived from the vasculature (see chap. 7). 

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