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Aflatoxin B₁ Metabolism to Aflatoxicol and Derivatives Lethal to Bacillus subtilis GSY 1057 by Rainbow Trout (Salmo gairdneri) Liver¹

Department of Food Science and Technology, Oregon State University, Corvallis, Oregon 97331

Aflatoxicol, R₀, was isolated from Mt. Shasta strain rainbow trout (Salmo gairdneri), and liver homogenates were incubated with aflatoxin B₁. Its identity was confirmed by mass, infrared, and ultraviolet spectrometry. The structure was identical to one of the diastereomers prepared by chemical reduction of aflatoxin B₁. Aflatoxicol was apparently formed by a reduced nicotinamide adenine dinucleotide phosphate-dependent soluble enzyme of the 105,000 x g supernatant from rainbow trout.

Aflatoxicol was not lethal in phosphate buffer to Bacillus subtilis GSY 1057 (metB4, hisA1, uvr-1) nor were aflatoxins B₁, Q₁, and B₂. In the presence of reduced nicotinamide adenine dinucleotide phosphate and trout liver microsomes, aflatoxicol reduced the viability of B. subtilis. Aflatoxin B₂, which lacks the vinyl ether present in the other compounds, could not be activated.

The product of aflatoxin B₁ activation by trout liver microsomes was sought after incubation of ¹⁴C-labeled aflatoxin B₁. The radioactivity was found in unaltered aflatoxin B₁ and in three extremely polar metabolites. The quantity of the new metabolites and the level of microbial lethality was reduced by addition of cytosine and cysteine to the incubation medium.

The vinyl ether configuration was a structural requirement for activation, and this finding and the nature of the enzymatic reaction were consistent with the hypothesis that the compounds were metabolized to highly reactive and unstable electrophilic products which bound to nucleophiles such as cytosine and were lethal to B. subtilis. The formation of aflatoxicol as the major product of trout liver metabolism is of great significance considering that it could be activated to a lethal compound and that rainbow trout are one of the most sensitive species to aflatoxin B₁-induced carcinoma.

¹ Technical Paper 4118, Oregon Agricultural Experiment Station. This Investigation was supported by USPHS Training Grant FD 00010 and Research Grants ES 00256 and ES 00541, United States Department of Health, Education, and Welfare.

² Present address: Department of Drug Metabolism, Searle Laboratories, Box 5110, Chicago, Ill. 60680. The material presented herein is taken in part from a dissertation submitted in partial fulfillment of the requirements for the Ph.D. in 1974.

³ Present address: Agricultural Research Center, Washington State University, Pullman, Wash. 99163.

⁴ Present address: University of Colorado Medical Center, Denver, Colo. 80220.

Received 10/23/75. Accepted 3/10/76.

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