The main applications of butadiene are synthetic rubber (SBR, SBS, thermoplastic rubber, etc.), widely used in producing shoe soles, tyres and other parts for the car industry, adhesives and sealants, asphalt and polymer modification and compounds for endless purposes.
We have previously shown that butadiene monoxide (BM), the primary metabolite of 1,3-butadiene, reacted with nucleosides to form alkylation products that exhibited different rates of formation and different stabilities under in vitro physiological conditions. In the present study, BM was reacted with single-stranded (ss) and double-stranded (ds) calf thymus DNA and the alkylation products were characterized after enzymatic hydrolysis of the DNA. The primary products were regioisomeric N-7-guanine adducts. N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine, which were depurinated from the DNA more rapidly than the N-7-guanine adducts, were also formed.
In addition, N6-(2-hydroxy-3-buten-1-yl)deoxyadenosine and N6-(1-hydroxy-3-buten-2-yl)deoxyadenosine were detected and evidence was obtained that these adducts were formed by Dimroth rearrangement of the corresponding N-1-deoxyadenosine adducts, not while in the DNA, but following the release of the N-1-alkylated nucleosides by enzymatic hydrolysis. N-3-(2-hydroxy-3-buten-1-yl)deoxyuridine adducts, which were apparently formed subsequent to deamination reactions of the corresponding deoxycytidine adducts, were also detected and were stable in the DNA. Adduct formation was linearly dependent upon BM concentration (10–1000 mM), with adduct ratios being similar at the various BM concentrations. At a high BM concentration (750 mM), the adducts were formed in a linear fashion for up to 8 h in both ssDNA and dsDNA. However, the rates of formation of the N-3-deoxyuridine and N6-deoxyadenosine adducts increased 10- to 20-fold in ssDNA versus dsDNA, whereas the N-7-guanine adducts increased only slightly, presumably due to differences in hydrogen bonding in ssDNA versus dsDNA. These results may contribute to a better understanding of the molecular mechanisms of mutagenesis and carcinogenesis of both BM and its parent compound, 1,3-butadiene.
When 1,3-butadiene is incubated with liver postmitochondrial fractions from mouse, rat, monkey or man and a NADPH-regenerating system, the formation rate of butadiene monoxide is different in the four species. With the exception of the rhesus monkey, the amount of epoxide is proportional to the monooxygenase activity. The sequence of epoxide formation is B6C3F1 mouse, Sprague Dawley rat, man, rhesus monkey. The ratio between mouse and monkey was about 7∶1. When 1,3-butadiene is incubated with homogenates from lung tissue, only tissues from mouse and rat produce measurable butadiene monoxide concentrations. The monooxygenase activity in lung tissue of the mouse was only 1/30 that in mouse liver. By contrast, lung tissue formed epoxide concentrations comparable to those formed by liver tissue, whereas monkey and human lung tissue did not produce any measurable levels of butadiene monoxide. The data might suggest that the results of recent rodent inhalation studies with 1,3-butadiene could not automatically be extrapolated to man.