The role of biotransformation in dietary (anti)carcinogenesis.
The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the (anti)carcinogenic potential of other compounds. This ambiguous theme is the basis for the present paper. The possible effects of enzymatic bioactivation and detoxification of dietary constituents are discussed using two representative examples of phase I and phase II biotransformation enzymes i.e., cytochrome P450 and glutathione S-transferase. Furthermore, the impact of genetic polymorphisms of these two enzyme systems is considered. Although it is very difficult on the basis of the enzyme inducing or inhibiting properties of dietary compounds, especially to characterize them as anticarcinogenic, for certain constituents it is acknowledged that they have anticarcinogenic properties. As such, this provides for an important mechanistic substantiation of the established cancer chemopreventive effect of a diet rich in fruits and vegetables.
WUR/TNO Centre for Food Toxicology, P.O. Box 8000, 6700 EA, Wageningen, The Netherlands. marlou.vaniersel@algemeen.tox.wau.nl
M L
ML
van Iersel
H
H
Verhagen
P J
PJ
van Bladeren
D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004032:Diet; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000517:prevention & control*; D015262:Xenobiotics / Q000493:pharmacokinetics
D002273:Carcinogens; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase