S. R. R. Musk

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

INTRODUCTION . . , 175 MECHANISMS OF CARCINOGENESIS . . 176 BLOCKING AGENTS . . 178 PHASE I METABOLISM ACTIVATION BY MONOOXYGENASES . . 178 Free radical mediated damage . . 180 Alternative route to phase I metabolism quinone reductase (QR) . . 181 C O N J U G A T I O N BY PHASE I1 ENZYMES . . 183 INDIRECT EFFECTS V I A ENTERIC BACTERIAL METABOLISM , . 184 INDUCERS OF D N A REPAIR . . 185 SUPPRESSING AGENTS . . 186 INHIBITORS OF CELL PROLIFERATION . . 186 Modijication of intracellular signalling . . . 187 Inhibition of oncogene expression . . . 188 Polyamine metabolism . . 188 Oestrogen metabolism . . 189 DIRECT A C T I N G MODULATORS OF CELL D A M A G E . . . 190 Suppression of free radical production . . . 190 Selective cytotoxins . . 191 I N D U C E R S OF C E L L U L A R DIFFERENTIATION . . 191 ANTIMETASTATIC AGENTS . . 192 IMMUNOMODULATION . . 192 A NEW CLASS OF NUTRIENTS?. . . 192 REFERENCES . . . 194

Genotoxic effects of crude juices from Brassica vegetables and juices and extracts from phytopharmaceutical preparations and spices of cruciferous plants origin in bacterial and mammalian cells

Crude juices of eight Brassica vegetables as well as juices and extracts of spices and phytopharmaceutical preparations from cruciferous vegetables were tested for induction of point mutations in Salmonella TA98 and TA100, repairable DNA damage in E.coli K-12 cells and clastogenic effects in mammalian cells. In bacterial assays, all juices caused genotoxic effects in the absence of metabolic activation, the ranking order being: Brussels sprouts > white cabbage > cauliflower > green cabbage > kohlrabi > broccoli > turnip > black radish. In experiments with mammalian cells, six juices induced structural chromosome aberrations. Brussels sprouts, white and green cabbage caused the strongest effects (800 microliters of juice induced a 5-fold increase over the background). In sister chromatid exchange assays, positive results were measured as well, but the effects were less pronounced. With all juices the genotoxic effects seen in mammalian cells were paralleled by a pronounced decrease in cell viability. Column fractionation experiments showed that 70-80% of the total genotoxic activity of the juices is found in the fraction which contains isothiocyanates and other breakdown products of glucosinolates, whereas phenolics and flavonoids contributed to a lesser extent to the overall effects. On the basis of these findings, and considering the negative results obtained with non-cruciferous vegetables (tomato, carrot and green pepper), it seems likely that the genotoxic effects of the juices are due to specific constituents of cruciferous plants such as glucosinolates and/or their breakdown products, in particular, isothiocyanates, which we found previously to be potent genotoxins in bacterial and mammalian cells. Finally, spices (mustards and horse radish paste) and phytopharmaceutical preparations were tested in bacterial assays. Mustards and horse radish caused very weak effects while most of the pharmaceutical preparations gave negative results, except cabbage tablets, which caused a strong and dose dependent induction of his revertants in Salmonella TA100. The present findings clearly indicate that cruciferous vegetables contain DNA damaging constituents. These observations are in contrast to earlier findings, which emphasized the antimutagenic effects of vegetable juices and also raise the question whether greatly increased consumption of Brassica vegetables or their concentrated constituents as a means for cancer prevention is indeed recommendable.

On the cytotoxicity and genotoxicity of allyl and phenethyl isothiocyanates and their parent glucosinolates sinigrin and gluconasturtiin

Four compounds commonly found in the human diet, allyl isothiocyanate (AITC), phenethyl isothiocyanate (PEITC) and their parent glucosinolates sinigrin and gluconasturtiin, were tested for cytotoxic and genotoxic effects in a Chinese hamster ovary cell line (CHO). The isothiocyanates were found to be more than one thousand times more cytotoxic than the glucosinolates, showing significant cytotoxic activity at concentrations below 1.0 microgram/ml. AITC was unable to induce either chromosome aberrations or sister chromatid exchanges (SCEs) even at highly cytotoxic doses. In contrast, PEITC was found to induce both aberrations and SCE at concentrations of 0.9-1.2 micrograms/ml whilst sinigrin and gluconasturtiin induced aberrations at concentrations above 2 mg/ml.

Induction of the anti-carcinogenic enzyme quinone reductase by food extracts using murine hepatoma cells

&NA; Over 145 extracts of vegetables, fruits, herbs, spices and beverages which are consumed regularly in the European diet have been surveyed for potential anti‐carcinogenic activity using an assay which measures the induction of NAD(P)H: (quinone acceptor) menadione oxidoreductase (quinone reductase, QR) activity in murine cells challenged with solutions of potential inducers. Where appropriate the study has included extracts prepared from cooked and autolysed material. The results indicate that extracts of some brassicas, legumes (peas), lettuces, red pepper, grapefruit and some herbs including basil, tarragon and rosemary are inducers of QR activity. Inducing activity is strongly dependent on processing and on variety.

Induction of glutathione S-transferase activity in hepG2 cells by extracts from fruits and vegetables

Abstract The human hepatoma cell line, hepG2, retains many of the xenobiotic metabolising enzymes found in normal hepatocytes, including an inducible glutathione S -transferase (GST). The isoform of GST that is induced by xenobiotics in this cell line is GSTA1-1. As a first step to determining the effect of diet on induction of GST in humans, we have examined the ability of extracts from a wide variety of fruits and vegetables to induce GST activity in hepG2 cells. Extracts from cruciferous vegetables (broccoli, Brussels sprouts, cabbage) were the most potent inducers, but this was dependent on the variety. Most of the extracts from fruits, with the exception of grapefruit, were poor inducers. Similarities and differences between the induction of GST and of quinone reductase in mouse hepalclc7 cells are discussed. The results show that extracts from cruciferous vegetables are effective inducers of human GST, in agreement with previous studies on GST in animals and cell lines derived from animals.