Reactivity of mutagenic propylene oxides with deoxynucleosides and DNA

Abstract

In an extension of previous studies with deoxycytidine and thymidine reactivities, propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide were reacted with deoxyguanosine as well as deoxyadenosine and, except for the trichloro compound, with DNA. Reactivity with the purine deoxynucleosides as well as the four deoxynucleosides in DNA were quantitated by HPLC methods. Correlations were found for the reactivity with individual deoxynucleosides in solution to Taft sigma electron-withdrawing values of the substituents on the epoxides and for reaction with model nucleophiles. In general, these correlations were not as pronounced for the reactivities of the propylene oxides with the nucleosides in DNA. Correlations for reactivity of the propylene oxides with the individual deoxynucleosides in solution and in DNA, except for dThd, were indicated for mutagenicity in TA100 in the liquid-preincubation Ames test. However, this was not the case for mutagenicities determined with the plate incorporation procedure nor with TA1535, where the relative mutagenicity of trichloropropylene oxide was the outstanding difference. Trichloropropylene oxide appeared to depend upon the error-prone system in TA100 for full expression of its mutagenicity.

DNA Interstrand Cross-Linking by Epichlorohydrin

“…However, there is evidence that ECH reacts with DNA, including binding covalently in vitro and in vivo (23)(24)(25)(26) as well as inducing DNA strand breaks (27,28). Studies with free bases have shown that ECH forms adducts prominently with N7 and O6 of guanine, and N6 and N3 of adenine (26,29,(30)(31)(32). Furthermore, ECH has been shown to cross-link proteins (33).…”

Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1‐naphthyl ether in mouse spleen cells in vivo

“…1980;Recio et al, 19901. We have been interested in structure-mutagenicity relationships for aliphatic epoxides [Wade et a]., 1978; Neau et al, 1982;Djuric et al, 1986;Rosman et al, 19881 and have found that after in vivo exposure of mice to four aliphatic epoxides-glycidyl 1 -naphthyl cther (GNE), 1 -naphthyl propylene oxidc, glycidyl 4-nitrophenyl ether, and trichloropropylene oxide (TCPO j t h e r e were significant dose-related incrcases in the frequencies of sister-chroniatid exchanges (SCE) and chromosome aberrations (CA) in bone marrow cells for all four epoxides [Giri et al. 19893. In order to study the mechanisms of mutation by which genotoxicity was induced in the mammalian cells by cpoxides, we are determining the types, distribution, and spectra of mutations at the molecular level induced in the coding 0 1993 Wiley-Liss, Inc. region of the hypoxanthine phosphoribosyl transferase (HPRT) gene.…”

1,2‐Epoxypropane [MAK Value Documentation, 2013]

“…In vitro 1,2-Epoxypropane binds covalently to calf thymus DNA (Djuric et al 1986;Randerath et al 1981;Solomon et al 1988). 1,2-Epoxypropane induces DNA damage and gene mutations in bacteria; it causes gene mutations in yeasts and fungi and mitotic gene conversion in Saccharomyces cerevisiae.…”