32P-Post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. II. Newborn male B6C3F1 mice

Abstract

When a series of nine alkenylbenzenes were administered to preweanling male mice, safrole, estragole and methyleugenol induced a significant incidence of hepatic carcinomas, while eugenol, anethole, elemicin, myristicin, dill apiol and parsley apiol did not (Miller et al., Cancer Res., 43, 1124-1134, 1983). Following the protocol used to test seven of these compounds, male C57Bl X C3H/He F1 mice were injected with 0.25, 0.5, 1.0 and 3.0 mumol of a compound on days 1, 8, 15 and 22 after birth, respectively. Groups of mice were killed and their liver DNA isolated on days 23, 29 and 43, and analysed by a modified 32P-post-labelling procedure. Highest levels of adducts were detected with methyleugenol (72.7 pmol/mg DNA), estragole (30.0) and safrole (17.5). After correction for liver growth it was estimated that most of these adducts were still present at 43 days. Significant levels of DNA binding by myristicin (7.8 pmol/mg DNA) and elemicin (3.7) were also found but in the former case the adducts were less persistent. Only low levels of adducts were detected with anethole, dill apiol and parsley apiol (less than 1.4 pmol/mg DNA); no DNA binding was detected with eugenol. Thus, all but one of the alkenylbenzenes studied became bound to newborn mouse-liver DNA, but the levels and the persistence of adducts formed by the carcinogenic compounds were greater.