Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk.
Enzymes of xenobiotic metabolism are involved in the activation and detoxification of carcinogens and can play a pivotal role in the susceptibility of individuals toward chemically induced cancer. Differences in such susceptibility are often related to genetically predetermined enzyme polymorphisms but may also be caused by enzyme induction or inhibition through environmental factors or in the frame of chemopreventive intervention. In this context, coffee consumption, as an important lifestyle factor, has been under thorough investigation. Whereas the data on a potential procarcinogenic effect in some organs remained inconclusive, epidemiology has clearly revealed coffee drinkers to be at a lower risk of developing cancers of the colon and the liver and possibly of several other organs. The underlying mechanisms of such chemoprotection, modifications of xenobiotic metabolism in particular, were further investigated in rodent and in vitro models, as a result of which several individual chemoprotectants out of the >1000 constituents of coffee were identified as well as some strongly metabolized individual carcinogens against which they specifically protected. This chapter discusses the chemoprotective effects of several coffee components and whole coffee in association with modifications of the usually protective glutathione-S-transferase (GST) and the more ambivalent N-acetyltransferase (NAT). A key role is played by kahweol and cafestol (K/C), two diterpenic constituents of the unfiltered beverage that were found to reduce mutagenesis/tumorigenesis by strongly metabolized compounds, such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, 7,12-dimethylbenz[a]anthracene, and aflatoxin B(1), and to cause various modifications of xenobiotic metabolism that were overwhelmingly beneficial, including induction of GST and inhibition of NAT. Other coffee components such as polyphenols and K/C-free coffee are also capable of increasing GST and partially of inhibiting NAT, although to a somewhat lesser extent.
Huber
Wolfgang W
WW
Institut für Krebsforchung, Department of Toxicology, Medical University of Vienna, Austria.
Parzefall
Wolfram
W
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D018890:Chemoprevention; D003069:Coffee / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry; D014453:Glucuronosyltransferase / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000517:prevention & control; D010636:Phenols / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D059808:Polyphenols; D011726:Pyridinium Compounds / Q000737:chemistry; D012307:Risk Factors; D000090264:UDP-Glucuronosyltransferase 1A9
D003069:Coffee; D004224:Diterpenes; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D059808:Polyphenols; D011726:Pyridinium Compounds; C011908:melanoidin polymers; C053401:kahweol; C014677:1-methylpyridinium; C053400:cafestol; D000123:Acetyltransferases; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione