Abstract 4630: Cruciferous vegetable glucosinolate hydrolysis products protect against Benzo[a]pyrene-induced genotoxicity

Abstract

Abstract Recent epidemiology studies have indicated that cruciferous vegetable intake is inversely correlated with lung cancer risk among smokers (Tang et al., BMC Cancer 2010, 10, 162). Benzo[a]pyrene (BaP) is a prominent contaminant of cigarette smoke, a model genotoxic carcinogen and powerful mutagen. Glucosinolates found in cruciferous vegetables are known to be hydrolysed to compounds that have been shown to be chemopreventive in both animal and cell-based systems, while, paradoxically, evidence is gathering that high concentrations of some of these hydrolysis products are genotoxic. The aim of the current study was to investigate whether pre-treatment of MCL-5 cells (a metabolically competent human lymphoblastoid cell line) with glucosinolate hydrolysis products conferred protection against the cytotoxicity and genotoxicity induced by a subsequent exposure to BaP. In the case of AITC (allyl isothiocyanate), a model glucosinolate hydrolysis product, toxicity and mutagenicity to MCL-5 cells was established for a range of concentrations. Mutagenicity was assessed through resistance to trifluorothymidine at the thymidine kinase (TK) locus and 6-thioguanine at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. The chemical treatments revealed a consistent trend for reduced cytotoxicity in cells pre-treated with AITC prior to BaP compared to those treated with BaP alone. Mutation frequency at the TK locus was consistently lower in the cells pre-treated with AITC compared to those treated with BaP alone. High concentrations of AITC induced a prolonged, dose-dependent cytotoxicity with cells only returning to normal growth rate after 7 days. These data suggest that pre-treatment of MCL-5 cells with glucosinolate hydrolysis products such as AITC affords protection against the genotoxic insult induced by mutagens such as BaP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4630. doi:10.1158/1538-7445.AM2011-4630