Dietary
phenethyl isothiocyanate (
PEITC) and a mixture of dietary
PEITC and
benzyl isothiocyanate (BITC) inhibit lung
tumorigenesis in A/J mice induced by a mixture of the tobacco
smoke carcinogens benzo[a]pyrene (B[a]P) and
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we tested the hypothesis that inhibition of
tumorigenesis by these
isothiocyanates was due to inhibition of
DNA adduct formation. We quantified the following pulmonary
DNA adducts: N2-[7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]
pyrene-10-yl]
deoxyguanosine (BPDE-N2-dG) from B[a]P; and
O(6)-methylguanine (O(6)-mG) and
4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts from NNK. Initial experiments demonstrated that there were no effects of B[a]P on NNK-
DNA adduct formation, or vice versa, and established by way of a time course study the appropriate sacrifice intervals for the main experiment. Dietary
PEITC, or dietary BITC plus
PEITC, inhibited the formation of HPB-releasing
DNA adducts of NNK at several of the time points examined. There were no effects of dietary
isothiocyanates on levels of O(6)-mG or
BPDE-N2-dG. These results, which are consistent with previous studies in rats and with
tumor inhibition data in mice, support a role for inhibition of HPB-releasing
DNA adducts of NNK as a mechanism of inhibition of
tumorigenesis by dietary
PEITC and BITC plus
PEITC. However, the observed inhibition was modest, suggesting that other effects of
isothiocyanates are also involved in
chemoprevention in this model.