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

Abstract

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 > or =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.

Are isothiocyanates potential anti-cancer drugs?

“…The coordinated nature of induction of phase 2 enzymes was studied in detailed in Wistar rats with BITC. BITC (0.5% (w/w) in the diet for 2 weeks) increased liver and small intestinal GST, QR and UDP-glucuronyl transferase activities by 1.7-to 11-fold [37] . BITC also increased GSH levels in the esophagus and small bowel of ICR/Ha mice by 63%−75% [38] .…”

Cruciferous vegetables and colo-rectal cancer

“…An extracolonic increase in phase 2 enzyme activity could protect the colon from carcinogens by reducing the delivery of partiallyactivated compounds from the systemic circulation (Pool-Zobel, 1999). Kassie et al (2002Kassie et al ( , 2003a have shown that in rodents exposed to the heterocyclic amine 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) the ability of juices prepared from cruciferous vegetables to protect against the induction of aberrant crypt foci (ACF) is correlated with their ability to increase the activity of the phase 2 enzyme UDP-glucuronosyl transferase form 2 in the liver. Cruciferous vegetables may also exert their protective effects through a local induction of phase 2 enzymes in the large intestine.…”

“…Other cruciferous vegetables have received relatively little attention. Single studies have found that garden cress (Lepidium sativum) juice and cruciferous seed meals and hulls are protective, whereas broccoli has been shown to have no effect (Barrett et al 1998;Rijken et al 1999;Kassie et al 2002). The latter finding of no protective effect of broccoli against azoxymethane-induced ACF is somewhat surprising because the breakdown products of glucobrassicin and glucoraphanin, the major GLS found in broccoli, have been shown to inhibit azoxymethaneinduced ACF Kim et al 2003).…”

Protective Effects of Epigallocatechin Gallate on Colon Preneoplastic Lesions Induced by 2-Amino-3-Methylimidazo(4,5-f)Quinoline in Mice

“…ACF are believed to be the earliest morphological alterations during the development of colonic mucosal neoplasia (15)(16)(17) and are used extensively to identify modulators of colon carcinogenesis. Indeed, the morphological and molecular features of ACF support the contention that ACF are putative preneoplastic lesions that can serve as biomarkers of colon cancer (18,19).…”