Aflatoxin mutagenicity

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. ... 

Stott, W.T. and Sinnhuber, R.O. Trout hepatic enzyme activation of aflatoxin-B] in a mutagen assay system and inhibitory effects of PCBs. Bull. Environ. Contam. Toxicol. (1978) 19, 35. 

Table IV. Effect of Casein Intake Upon Conversion of Aflatoxin B] by Trout PMF to a Mutagen for Salmonella...

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 ... 

Figure 4. Toxic and mutagenic response of diploid human lymphoblast line MIT-2 to aflatoxin B,. Open symbols afatoxin + phenobarbital-induced rat liver postmitochondrial supernatant (PMS) closed symbols effect of treatment with either aflatoxin or FMS alone.

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... 

TAIOO vs aflatoxin Bl-induced mutagenesis " . Asafoetida, on agar plate, was active on Salmonella typhimurium TAIOO and TA1535 microsomal activation-depen-dent mutagenicity of 2-acetamidofluo-rene """. 

Garg, D. K., A. C. Banerjea, and J. Verma. The role of intestinal Clostridia and the effect of asafetida (Hing) and alcohol in flatulence. Indian J Microbiol 1980 20(3) 194-197. Bordia, A., and S. K. Arora. The effect of essential oil (active principle) of asafetida on alimentary lipemia. Indian J Med Res 1975 63(5) 707-711. Soni, K. B., M. Lahiri, P. Chakcradeo, S. V. Bhide, and R. Kuttan. Protective effect of food additives on aflatoxin-induced mutagenicity and hepatocar-cinogenicity. Chem Lett 1997 115(2) 129-133. 

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. 

Goeger, D.E., Hsie, A.W. Anderson KE. (1999) Co-mutagenicity of coumarin (1,2-benzo-pyrone) with aflatoxin B1 and hnman liver S9 in mammalian cells. Food chem. Toxicol., 37, 581-589... 

Application of relative activity factors to aflatoxin b, mutagenicity data prediction of... 

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.

Simula, T.P, Glancey, M.J. Wolf, C.R. (1993) Human glutathione S -transferase-expressing Salmonella typhimurium tester strains to study the activation/detoxification of mutagenic compounds studies with halogenated compounds, aromatic amines and aflatoxin Bp Carcinogenesis, 14, 1371-1376... 

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. 

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). 

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