CYTOGENETIC EFFECTS OF BUTADIENE METABOLITES IN RAT AND MOUSE SPLENOCYTES FOLLOWING IN-VITRO EXPOSURES

As a first step in investigating the genotoxic effects of the principa l metabolites of 1,3-butadiene (ED) in both rats and mice, splenocytes (which have little mixed function oxidase activity) from each specime n were exposed to a series of concentrations of either 3,4-epoxy-1-but ene (EB) (20 to 931 mu M) or 1,2:3,4-diepoxybutane (DEB) (2.5 to 160 m u M) for 1 h. The splenocytes were then washed, cultured, and stimulat ed to divide with concanavalin A, and metaphases were analyzed for the induction of sister chromatid exchanges (SCEs) and chromosome aberrat ions (CAs). In addition, cells from some experiments were taken after exposure but before culture, and subjected to the single cell gel (SCG ) assay to measure DNA damage in the form of DNA strand breakage and/o r alkaline-labile sites. Initial studies indicate that EB does not ind uce cytogenetic damage in either rat or mouse G(0) splenocytes. Howeve r, DEB was an extremely potent SCE- and CA-inducer in both species wit h no species differences apparent. Neither DEB nor EB produced any sta tistically significant DNA-damaging effects as measured by the SCG ass ay.