Mutagenicity of aryl propylene and butylene oxides with Salmonella

Abstract

10 aryl propylene oxides and 6 aryl butylene oxides were synthesized. Dose-mutagenicity relationships were studied for these compounds and for 1,2-epoxybutane, using both the preincubation and plate incorporation Ames tests with Salmonella typhimurium strains TA100 and TA1535. Structure-mutagenicity relationships were further examined by concurrent testing at single doses with the plate incorporation assay in strain TA100. In both series of compounds, mutagenicity showed very correlation to chemical reactivity, molar volume and partition values. However, all compounds were mutagenic in at least one system with the propylene oxides being more mutagenic than the corresponding butylene oxide derivatives. The naphthyl derivatives in each series were the most mutagenic.

Mutagenicity of oxaspiro compounds with Salmonella

“…Among the model oxaspiro compounds, the weakest alkylating agent in the present series, cyclohexylidene oxide, is stronger than the 1,2-disubstituted epoxides cyclohexene oxide (0.024 + 0.003) and cyclopentene oxide (0.011_ 0.002) while the trichothecene, anguidine, was inactive (0.003 + 0.003) when run under the same conditions. Although the alkylating ability of the oxaspiro compounds is in the same order of magnitude as our previous series of 1,1-disubstituted epoxides, the para-substituted ct-methylstyrene oxides (Rosman et al, 1986), they are less active in this regard than the monosubstituted propylene and butylene oxides (Rosman et al, 1987) or the glycidyl ethers (Rosman et al, 1988).…”

“…As we have previously observed with monosubstituted epoxides (Rosman et al, 1987(Rosman et al, , 1988, relative reactivity with 4-(4-nitrobenzyl)pyridine is not a reliable predictor of mutagenicity within the present oxaspiro series. Certainly, the relative polarity of these compounds has to be considered.…”

Chromosomal aberrations in mouse lymphocytes exposed in vivo and in vitro to aliphatic epoxides

“…Because these epoxides can be strong alkylating agents, their in vitro mutagenicity and in vivo genotoxicity is of interest (Manson, 1980;Ehrenberg and Hussain, 1981). The present study is an extension of our previous investigations of structure-mutagenicity and in vivo genotoxicity relationships for aliphatic epoxides (Wade et al, 1978;Neau et al, 1982;Djuric et al, 1986;Rosman et al, 1987Rosman et al, , 1988Giri et al, 1989Giri et al, , 1990).…”

“…1,2-Epoxy-3-(p-nitrophenoxy)propane [5255-75-4] (glycidyl 4-nitrophenyl ether, GNPE) was obtained from Eastman Kodak Co. (Rochester, NY) and purified by repeated recrystallization from ethanol. Glycidyl 1-naphthyl ether [2461-42-9] (GNE) and 1-naphthylpropylene oxide [68884-32-2] (NPO) were prepared in this laboratory (Rosman et al, 1987).…”

Base‐pair mutations caused by six aliphatic epoxides in salmonella typhimurium TA100, TA104, TA4001, and TA4006

“…In an extension of our interest in structure-mutagenicity relationships of aliphatic epoxides [Wade et al, 1978;Neau et al, 1982;Djuric et al, 1986;Rosman et al, 1986Rosman et al, , 1987Rosman et al, , 1988. we wished to characterize base-pair mutations in model epoxides by phenotypic screening.…”