Journal Article

Chemoprotective effects of garden cress (<i>Lepidium sativum</i>) and its constituents towards 2-amino-3-methyl-imidazo[4,5-<i>f</i>]quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions

Fekadu Kassie, Sylvie Rabot, Maria Uhl, Wolfgang Huber, Hong Min Qin, Christoph Helma, Rolf Schulte-Hermann and Siegfried Knasmüller

in Carcinogenesis

Volume 23, issue 7, pages 1155-1161
Published in print July 2002 | ISSN: 0143-3334
Published online July 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.7.1155
Chemoprotective effects of garden cress (Lepidium sativum) and its constituents towards 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions

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The chemoprotective effect of garden cress (GC, Lepidium sativum) and its constituents, glucotropaeolin (GT) and benzylisothiocyanate (BITC), a breakdown product of GT, towards 2-amino-3-methyl-imidazo [4,5-f] quinoline (IQ)-induced genotoxic effects and colonic preneoplastic lesions was investigated in single cell gel electrophoresis (SCGE) assays and in aberrant crypt foci (ACF) experiments, respectively. Pretreatment of F344 rats with either fresh GC juice (0.8 ml), GT (150 mg/kg) or BITC (70 mg/kg) for three consecutive days caused a significant (P < 0.05) reduction in IQ (90 mg/kg, 0.2 ml corn oil/animal)-induced DNA damage in colon and liver cells in the range of 75–92%. Chemical analysis of GC juice showed that BITC does not account for the effects of the juice as its concentration in the juice was found to be 1000-fold lower than the dose required to cause a chemoprotective effect. Parallel to the chemoprotection experiments, the modulation of the activities of cytochrome P4501A2, glutathione-S-transferase (GST) and UDP glucuronosyltransferase (UDPGT) by GC juice, GT and BITC was studied. Whereas GT and BITC did not affect the activity of any of the enzymes significantly, GC juice caused a significant (P < 0.05) increase in the activity of hepatic UDPGT-2. In the ACF assay, IQ was administered by gavage on 10 alternating days in corn oil (dose 100 mg/kg). Five days before and during IQ treatment, subgroups received drinking water which contained 5% cress juice. The total number of IQ-induced aberrant crypts and ACF as well as ACF with crypt multiplicity of ≥4 were reduced significantly (P < 0.05) in the group that received IQ plus GC juice compared with the group that was fed with IQ only. However, crypt multiplicity was not significantly different in these two groups when all ACF with all classes of crypt multiplicity were considered in the analysis. This is the first report on the inhibition of HA-induced DNA damage and preneoplastic lesions by a cruciferous plant. Our findings suggest that the chemoprotective effect of GC is mediated through enhancement of detoxification of IQ by UDPGT.

Keywords: ACF, aberrant crypt foci; IQ, 2-amino-3-methylimidazo [4,5-f] quinoline; BITC, benzyl isothiocyanate; GC, garden cress; GS, glucosinolate; GT, glucotropaeolin; GST, glutathione-S-transferase; HAs, heterocyclic amines; ITC, isothiocyanate; SCGE, single cell gel electrophoresis assay; UDPGT, UDP glucuronosyltransferase

Journal Article.  6158 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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