Journal Article

Effects of benzyl isothiocyanate and 2-phenethyl isothiocyanate on benzo[<i>a</i>]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism in F-344 rats

Gunnar Boysen, Patrick M.J. Kenney, Pramod Upadhyaya, Mingyao Wang and Stephen S. Hecht

in Carcinogenesis

Volume 24, issue 3, pages 517-525
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.517
Effects of benzyl isothiocyanate and 2-phenethyl isothiocyanate on benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism in F-344 rats

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

A mixture of dietary benzyl isothiocyanate (BITC) and 2-phenethyl isothiocyanate (PEITC) inhibits lung tumorigenesis by a mixture of benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. Previous studies indicated that inhibition of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) releasing DNA adducts of NNK by PEITC in the lung was responsible for inhibition of tumorigenicity. We have now extended these investigations to F-344 rats treated with 2 p.p.m. B[a]P in the diet and 2 p.p.m. NNK in the drinking water. The effects of BITC (1 μmol/g diet), PEITC (3 μmol/g diet), and a mixture of BITC plus PEITC (1 and 3 μmol/g diet) on DNA and hemoglobin (Hb) adducts of B[a]P and NNK, and on two urinary metabolites of NNK, were examined. DNA adducts were quantified after 8 and 16 weeks of treatment. Hb adducts were quantified in blood samples withdrawn every 2 weeks. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide NNAL-Gluc were measured in urine every 4 weeks. PEITC or BITC plus PEITC significantly reduced levels of HPB releasing DNA adducts of NNK in lung at 8 and 16 weeks, but there was no effect of BITC. There were no effects of any of the treatments on levels of HPB releasing DNA adducts of NNK in liver, or on DNA adducts of B[a]P in either lung or liver. PEITC or BITC plus PEITC significantly inhibited the formation of Hb adducts of NNK from 2–12 weeks of treatment while there were no effects on Hb adducts of B[a]P. There was a significant increase in levels of NNAL and NNAL-Gluc in the urine of the rats treated with PEITC or BITC plus PEITC. These results demonstrate that dietary PEITC, or a mixture of BITC plus PEITC, inhibit the formation of HPB releasing adducts of NNK in the rodent lung, leading to inhibition of tumorigenesis.

Keywords: B[a]P, benzo[a]pyrene; BITC, benzyl isothiocyanate; BPDE, (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-benzo[a]pyrene; BPDE-N2-dG, N2-[7,8,9-trihydroxy-7,8,9,10-tetrahydro-10-yl]deoxyguanosine; GC-NICI-MS, gas chromatography-negative ion chemical ionization-mass spectrometry; Hb, hemoglobin; HPB, 4-hydroxy-1-(3-pyridyl)-1-butanone; iso-NNAL, 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; P450, cytochrome P450; PEITC, 2-phenethyl isothiocyanate; RBC, red blood cells; trans/anti-B[a]P-tetraol, r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; trans/anti-B[a]P-TME, r-7,t-8,9,c-10-tetramethoxy-7,8,9,10-tetrahydrobenzo[a]pyrene

Journal Article.  7556 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.