Concurrent with the increase in our knowledge of the genetic and environmental factors that lead to glucosinolate accumulation in plants, and the role of these compounds and their derivatives in mediating plant-herbivore interactions, there has been significant advances in our understanding of how glucosinolates and their products may contribute to a reduction in risk of carcinogenesis and heart disease when consumed as part of the diet. In this paper, we review the epidemiological evidence for the health promoting effects of cruciferous vegetables, the processes by which glucosinolates and isothiocyanates are absorbed and metabolised by humans, with particular regard to the role of glutathione S-transferases, and the biological activity of isothiocyanates towards mammalian cells and tissues.

GSTM1 genotypes have a significant effect on the metabolism of sulforaphane derived from standard or high-glucosinolate broccoli. It is possible that the difference in metabolism may explain the greater protection that GSTM1-positive persons gain from consuming broccoli. The potential consequences of consuming glucosinolate-enriched broccoli for GSTM1-null and -positive persons are discussed.

Broccoli florets contain low levels of 3-methylsuphinylpropyl and 4-methylsulphinylbutyl glucosinolates. Following tissue disruption, these glucosinolates are hydrolysed to the corresponding isothiocyanates (ITCs), which have been associated with anticarcinogenic activity through a number of physiological mechanisms including the induction of phase II detoxification enzymes and apoptosis. In this paper, we describe the development of ITC-enriched broccoli through the introgression of three small segments of the genome of Brassica villosa, a wild relative of broccoli, each containing a quantitative trait locus (QTL), into a broccoli genetic background, via marker-assisted selection and analysis of glucosinolates in the florets of backcross populations. Epistatic and heterotic effects of these QTLs are described. The ITC-enriched broccoli had 80-times the ability to induce quinone reductase (a standard assay of phase II induction potential) when compared to standard commercial broccoli, due both to an increase in the precursor glucosinolates and a greater conversion of these into ITCs.

Significant differences occur in the levels and types of aliphatic glucosinolates in leaves of plants of four Brassica oleracea populations in Dorset. Plants in grassland at St Aldhelm's Head and Winspit have high levels of 3-butenyl glucosinolate, whereas plants of an adjacent population growing on and along the top of cliffs at Kimmeridge have low levels of 2-hydroxy-3-butenyl, 2-propenyl and methylsuiphinylalkyl glucosinolates. Plants growing in a variable habitat at Worbarrow Tout have intermediate levels. The differences in occurrence of individual glucosinolates result from allelic variation at four loci. The level of total aliphatic glucosinolates is under more complex genetic control, but is shown to be highly heritable. Allele frequencies at isozyme loci indicate that genetic variation for glucosinolate production is unlikely to have arisen or to be maintained by founder effects or genetic drift. It is suggested that there is selection for high levels of butenyl glucosinolates at St Aldhelm's Head and Winspit because of grazing by generalist herbivores, whereas there is selection for low levels of 2-hydroxy-3-butenyl and other non-butenyl aliphatic glucosinolates at Kimmeridge because of two factors. First, plants effectively escape from generalist herbivores because of physical aspects of the habitat and association with other plant species which provide physical and chemical defences. Thus there is selection for individuals which do not carry the hypothetical metabolic costs of glucosinolate biosynthesis. Secondly, herbivory by specialist cruciferous insects at Kimmeridge, which is enhanced because of the local abundance of B. nigra, selects for individuals which have low levels of 2-hydroxy-3-butenyl glucosinolates.

No abstract

No abstract

The inheritance of aliphatic glucosinolates in Arabidopsis thaliana was studied. Analysis of F3 families from a cross between the ecotype Limburg-5 and the accession H5 1 (an inbred line derived from the ecotype Stockholm) suggested that alleles at a single locus regulate the conversion of methylsuiphinylalkyl glucosinolates into alkenyl (and hydroxyalkenyl) glucosinolates. Likewise, analysis of recombinant inbred lines derived from a cross between the ecotypes Columbia and Landsberg erecta suggested that alleles at a single locus regulate the conversion of methylsulphinylpropyl glucosinolate into hydroxypropyl glucosinolate. Both loci mapped to a similar position on chromosome 4 and it is suggested that these alleles occur at the same locus. A genetic model is proposed in which the aliphatic glucosinolates of A. thaliana are determined by alleles at three loci. The ecological significance of variation in aliphatic glucosinolates is discussed.

Sulforaphane (SF), a dietary phytochemical obtained from broccoli, has been implicated in several physiological processes consistent with anticarcinogenic activity, including enhanced xenobiotic metabolism, cell cycle arrest, and apoptosis. In this study, we report changes in global gene expression in Caco-2 cells exposed to physiologically appropriate concentrations of SF, through the use of replicated Affymetrix array and RT-PCR experiments. After exposure to 50 micromol/L SF, 106 genes exhibited a >2-fold increase in expression and 63 genes exhibited a >2-fold decrease in expression. There were fewer changes in gene expression at lower SF concentrations. The majority of these genes had not previously been shown to be modulated by SF, suggesting novel mechanisms of possible anticarcinogenic activity, including induction of differentiation and modulation of fatty acid metabolism. The changes in the expression of 10 of these genes, together with 4 additional genes of biological interest, were further quantified in independent studies with RT-PCR. These genes include several that have recently become associated with carcinogenesis, such as Krüppel-like factor (KLF)4, a gut-enriched transcription factor associated with induction of differentiation and reduction in cellular proliferation; DNA (cytosine-5-)-methyltransferase 1, associated with methylation; and alpha-methylacyl-CoA racemase (AMACR), a marker associated with the development of colon and prostate cancer. The expression of 5 of these genes [caudal type homeo box transcription factor 2 (CDX-2), KLF4, KLF5, cyclin-dependent kinase inhibitor 1A (p21), and AMACR] was additionally studied after in vitro exposure to SF of surgically resected healthy and cancerous colon tissue from each of 3 patients. The study suggests the complex effects that SF has on gene expression and highlights several potential mechanisms by which the consumption of broccoli may reduce the risk of carcinogenesis.