ABSTRACT
The effects of green tea on the metabolism of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) with emphasis on the formation of the detoxified glucuronides was studied. Two groups of 20 adult male and female Fischer 344 rats consumed 2% green tea or water for 6 weeks before being administered a single dose of 40 mg/kg body weight of [2-14C]IQ by oral gavage. Major metabolites in 24 h urine samples were separated by high-performance liquid chromatography (HPLC), including N-OH-IQ-N-glucuronide, 5-OH-IQ glucuronide and sulfate, IQ sulfamate and IQ itself. The structures of the main metabolites were established by mobility on the HPLC and by mass spectrometry. Sulfate esters and sulfamate were hydrolyzed by 0.1 N HCl for 15 min at 100 degrees C, yielding 5-OH-IQ and high levels of IQ. HPLC of the resulting product showed the N-OH-IQ-N-glucuronide and the 5-OH-IQ glucuronide, as well as IQ. The male and female rats drinking tea displayed a significantly higher (P < 0.05) excretion of the two major glucuronides. We conclude that intake of green tea increases the excretion of N-OH-IQ-N-glucuronide, a detoxified metabolite of the proximate carcinogen N-OH-IQ.
Subject(s)
Carcinogens/pharmacokinetics , Glucuronides/urine , Quinolines/urine , Tea/chemistry , Animals , Chromatography, High Pressure Liquid , Female , Male , Rats , Rats, Inbred F344 , Spectrometry, Mass, Electrospray IonizationABSTRACT
The effects of green tea intake on the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat was studied. IQ belongs to a new class of mutagens and carcinogens, heterocyclic arylamines, formed during cooking through browning meats and fish, thus, in the food chain of most non-vegetarians. Ten adult male and female Fischer 344 rats were placed on a 2% solution of green tea and 10 control rats were on water for 6 weeks. Then, animals were administered a single dose of 40 mg/kg body weight of [2-14C]IQ by oral gavage. Twenty-four hour urine samples were collected and metabolites were separated by HPLC and quantitated by scintillation counting. Two minor and three major metabolites were isolated, including, small quantities of IQ itself. The rats on tea showed significant differences (P < 0.05) in the recovery of the three major metabolites, namely, IQ-sulfamate, IQ-5-O-sulfate, and IQ-5-O-glucuronide, respectively. Green tea, therefore, influences the manner in which the food carcinogen IQ is metabolized and excreted in urine. Formation of glucuronides, increased by green tea, represent a key means of detoxification of the heterocyclic amine, IQ.
