Carcinogens/mutagens aflatoxin

Aflatoxins are potent carcinogenic, mutagenic and teratogenic metabolites produced by molds. The major food affected with aflatoxins are corn, peanuts, rice, cottonseeds, dried fruit and milk from ingestion (103). The US action standards established by FDA are 20 pg/Kg for foods consumed by humans and 0.5 pg/kg for milk. In the case of animal feed, the levels are from 100 to 300 pg/kg. Therefore, assays capable of detecting at these levels have to be developed, (see Table 1 (104,105)). Detection of aflatoxins entails conjugation of these small molecules with carrier proteins like bovine serum albumin to produce antibodies (20). A number of commercial kits for aflatoxins are available (see sections on kits and immunoaflinity purification). 

It has been found that melanoidins are antagonistic to mutagens and such carcinogens as aflatoxin B and N-methyl-N -nitro-AT-nitrosoguanidine and various heterocyclic mutagens. High-molecular-weight fractions of melanoidin are the most effective in this respect." ... 

Aflatoxins, Aspergillus flavus and A. parasiticus metabolites, can be carcinogenic, mutagenic, teratogenic and toxic. Zinc is required for auxin synthesis and therefore, both plant growth and development. Cultivars (cvs). of Zea mays seedlings vary in aflatoxin (AFBi)... 

Work in my laboratory has been supported by grants from the NIH. I am indebted to many of my present and former colleagues, in particular to Drs. A.J. Warren and P.L. Foster for their work on the mutagenic specificity of chemical carcinogens and to Dr. J.H. Miller for his collaborative effort in studying the mutagenic specificity of benzola]pyrene and aflatoxin B. ... 

Afiatoxin is one of the most mutagenic and carcinogenic natural compounds described to date. Traditional methods for the measurement of aflatoxins fall into two groups ... 

Electron-rich alkenes are the more reactive jr-bond snbstrates towards epoxidation by the electrophilic dioxiranes Some typical examples of these oxidations are snm-marized in Scheme 2. Since the resnlting epoxides are nsnally hydrolytically and ther-molytically qnite labile, snch oxidations are best carried ont with isolated dioxiranes. For example, the 8,9 epoxide of the well-known aflatoxin B, postnlated as potent carcinogen in the oxidative metabolism of this natural product, escaped numerous efforts to prepare it by conventional epoxidations because of its sensitivity towards hydrolysis . The synthesis of this labile epoxide was readily accomplished by employing a solution of the isolated DMD at room temperature (equation 2), and its mutagenicity unequivocally... 

FA088 Soni, K. B., M. Lahiri, P. Chackradeo, S. V. Bhide, and R. Kuttan. Protective effect of food additives on aflatoxin-induced mutagenicity and hepato-carcinogenicity. Cancer Lett 1997 115(2) 129-133. 

Figure 6.55 Log-log plot of relative carcinogenic potencies for a group of chemicals against mutagenic potency as determined by the Ames test. The potency is the amount of chemical giving tumors in 50% of the animals or 100 mutant colonies (revertants) of Salmonella bacteria. Aflatoxin B, is the most potent and benzidine the least potent. Abbreviations Moca, 4,4,-methylene-b/s-(2-chloroaniline) mms, methylmethane sulfonate. Source From Ref. 16.

The carcinogenic aflatoxins, which are produced by Aspergillus flavus, may be present in infected peanuts and other foodstuffs.790 Like many other compounds that are carcinogenic or mutagenic, the aflatoxins are not unusually reactive chemically. 

The adverse health effects most readily associated with mycotoxin consumption are either acute or subchronic. Chronic effects, such as carcinogenicity, have been more difficult to directly relate to mycotoxin consumption. This is in spite of the fact that various data indicate that at least 45 mycotoxins are known to be either mutagenic or carcinogenic (1). The following mycotoxins may pose an adverse human health risk in respect to carcinogenicity aflatoxin, cyclochlorotine, griseofulvin, luteoskyrin, ochratoxin, patulin, penicillic acid, sterigmatocystin, T-2 toxin, and zearalenone. 

Aflatoxin A. flavus A. parasiticus apoptosis mutagen hepatotoxin carcinogen teratogen acute aflatoxicosis, hepatocarci nogenesis, childhood cirrhosis. Rye s syndrome... 

Since the discovery of the Turkey X disease in 1960, aflatoxins have been established as mutagenic, teratogenic and hepatocarcinogenic in experimental animals. AFB] is the most toxic of this group of toxins and the order of toxicity is Bi>Gi>B2>G2. Aflatoxin M] is 10-fold less toxic than Bj, but its presence in milk is of concern in human health [66-68]. AFBj is also one of the most carcinogenic natural compounds known therefore, extensive research has been done on its synthesis, toxicity and biological effects [53, 69-72]. 

A key feature of this detection system is the inclusion of a mammalian liver homogenate (Section 4.1.2). Recall that some potential carcinogens such as aflatoxin are converted into their active forms by enzyme systems in the liver or other mammalian tissues (Section 27.6.1). Bacteria lack these enzymes, and so the test plate requires a fe-w milligrams of a liver homogenate to activate this group of mutagens. 

In 1960-63, the death of turkeys in England (referred to as turkey X disease) was associated with the consumption of peanut meal feeds containing aflatoxins. Death usually occurs from hepatoxicity. Aflatoxin Bj is carcinogenic to a wide variety of animal species rats are particularly sensitive to this effect. It is also mutagenic and teratogenic in rodents. 

---