Fava beans are prominent in the diet of the Colombian population at high
gastric cancer risk. Upon
nitrite treatment under simulated gastric conditions, a potent
mutagen was formed as detected by a forward mutation assay using Salmonella typhimurium TM677 without microsomal activation. The promutagen was partially purified by preparative t.l.c. and normal phase h.p.l.c. of the
acetone-soluble portion of a dried aqueous extract. The nitrosated promutagen fully accounted for the mutagenicity observed with whole fava beans. One gram of fresh fava beans yielded approximately 0.35 nmol of
mutagen. Mutagenicity data indicated that this
mutagen was more potent than
N-methyl-N'-nitro-N-nitrosoguanidine. The characteristics of the
mutagen were typical of an activated N-nitroso compound, that is a compound in which the N-nitroso moiety is attached to an activating group, such as a carbonyl group. Irradiation of the
mutagen yielded a Griess positive reaction. By reverse-phase h.p.l.c. photohydrolysis, a single peak could be ascribed to the
mutagen. Its stability varied as a function of pH, being most unstable under alkaline conditions.
Cysteine and
phosphate concentration had no effect on its rate of decomposition, thereby strongly suggesting that the
mutagen is an N-nitrosourea. The results obtained in this study support the hypothesis of
carcinogenesis via the intragastric production of activated N-
nitroso compounds.