Journal Article

Effects of benzyl isothiocyanate and phenethyl isothiocyanate on DNA adduct formation by a mixture of benzo[<i>a</i>]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung

Kristina R.K. Sticha, Patrick M.J. Kenney, Gunnar Boysen, Hong Liang, Xiaojing Su, Mingyao Wang, Pramod Upadhyaya and Stephen S. Hecht

in Carcinogenesis

Volume 23, issue 9, pages 1433-1439
Published in print September 2002 | ISSN: 0143-3334
Published online September 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.9.1433
Effects of benzyl isothiocyanate and phenethyl isothiocyanate on DNA adduct formation by a mixture of benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung

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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 O6-methylguanine (O6-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 O6-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.

Keywords: B[a]P, benzo[a]pyrene; B[a]P-tetraols, r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, r-7,t-8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, r-7,t-8,10,c-9-tetrahydroxy-7,8,9,10-tetrahydrobenzo-[a]pyrene, and r-7,t-8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; BITC, benzyl isothiocyanate; BPDE, 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene; BPDE-N2-dG, N2-[7,8,9-trihydroxy-7,8,9,10-tetra-hydrobenzo[a]pyrene-10-yl]deoxyguanosine; GC-NICI-MS, gas chromatography-negative ion-chemical ionization mass spectrometry; HPB, 4-hydroxy-1-(3-pyridyl)-1-butanone; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; O6-mG, O6-methylguanine; PEITC, phenethyl isothiocyanate

Journal Article.  6144 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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