Metabolic activation of 1,2-dibromo-3-chloropropane to mutagenic metabolites: detection and mechanism of formation of (Z)- and (E)-2-chloro-3-(bromomethyl) oxirane

摘要: 1,2-Dibromo-3-chloropropane (DBCP), a haloalkane nematocide and soil fumigant, is metabolically activated to chemically reactive species that are direct-acting mutagens in Salmonella typhimurium TA 100 test system. Studies vitro with rat liver microsomes indicated oxidation at carbon 3 resulted the formation of an unstable gem-chlorohydrin rearranged elimination hydrogen bromide form (Z)-2-chloro-3-(bromomethyl)oxirane [(Z)-CBPO] (E)-2-chloro-3-(bromomethyl)oxirane [(E)-CBPO]. Gas chromatography-mass spectrometry (GC-MS) positive ion chemical ionization (CI) was employed identify (Z)-CBPO (E)-CBPO by comparison characteristic fragment ions their CI mass spectra those observed for authentic standards. Quantitative GC-MS methodology exploited quantitate rate from DBCP analogues specifically deuterated 1 3. The Z- E-isomers CBPO 31 33 pmol/(min.mg protein), respectively, DBCP; substitution deuterium increased epoxide 50%, whereas could not be detected substrate labeled Both epoxides were directly acting S. 100. caused approximately twice as many his+ revertants/nmol compared (E)-CBPO. Oxidation 2 bifunctional alkylating agent, 1-bromo-3-chloroacetone, presumably via intermediacy gem-bromohydrin.(ABSTRACT TRUNCATED AT 250 WORDS)