Alkylating and Mutagenic Effects of Allyl and Allylogenic Compounds

Abstract

Some allyl compounds have been found active, others inactive in carcinogenicity testing in intact animals. The carcinogenic activity has been attributed, up to now, to the possible epoxidation of the olefinic moiety in these molecules. However, allylic or allylogenic structures are generally characterized by a rather strong SN-1 as well as SN-2 reactivity; they may alkylate nucleophilic biomolecules and thus initiate chemical carcinogenesis and mutagenesis. We investigated the direct alkylating properties of a series of allyl and allylogenic compounds and tested their mutagenic potential in an in vitro-bacterial testing system (A) (Ames et al., Proc.Natl.Sci.70, 2281; 1973). — The selection of compounds was guided by theoretical evaluation of the influence of various substituents on the reactivity of the molecules. These alkylating properties were determined by reaction with 4-nitrobenzyl pyridine (B). Positive results in A and B were found with: allyl chloride, allyl cyanide, 1-chloro-2-methyl-2-propene, 1-chloro-2-butene; negative, in both tests (A and B) were allyl amine and diallyl sulfide. With allyl alcohol, a high mutagenic potential (A) did not correlate with a negative result in B; this, however, might be due to the fact that OH, under the condition of test, does not represent a good leaving group. These findings clearly indicate the possibility that allyl compounds might exert a direct carcinogenic effect. Whether or not this competes with an epoxidation as an indirect activating mechanism is due to further investigations.