HEMOGLOBIN ADDUCTS FROM ISOPRENE AND ISOPRENE MONOEPOXIDES

1. Isoprene is metabolised in vitro by oxygenation of either double bo nd to 2-ethenyl-2-methyloxirane (epoxide A) and 2-(1'-methylethenyl)ox irane (epoxide B). The reactivity in vitro and formation in vivo of th e monoepoxides of isoprene were studied by the formation of adducts to N-terminal valines in haemoglobin (Hb). These adducts were analysed b y mass spectrometry after cleavage and derivatization by a modified Ed man degradation method. 2. When red blood cells were incubated with co mmercial isoprene oxide (about 95 % epoxide A, less than or equal to 5 % epoxide B) adducts from both epoxides were formed. 3. It is confirm ed that epoxide A is hydrolysed much faster than epoxide B. The rates are enhanced by phosphate buffer (epoxide A), probably through acid ca talysis, and by the presence of red blood cells (both epoxides), due t o enzymatic detoxification. 4. Comparison of total valine adduct level s in Hb from isoprene and isoprene oxide injected i.p. led to the conc lusion that 23 and 1 % of injected isoprene was metabolized to the epo xides in mouse and rat, respectively.