The role of tea on the metabolism of the food carcinogen 2-amino-3-methylimidazo[4,5-F]quinoline (IQ)

The main purpose of this dissertation research is to establish a detoxification metabolic pathway for the food carcinogen 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) in the F344 rat, which is upregulated by green tea.;The effects of green tea on the metabolism of the food carcinogen 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) in the F344 rat were studied. Two groups of twenty adult male and female Fischer 344 rats consumed 2% green tea or water for 6 weeks before being administered single doses 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 high-performance liquid chromatography (HPLC), and quantitated by scintilation counting. One minor and four major metabolites were isolated in both groups of animals, including small quantities of the unmetabolized IQ. The minor metabolite was identified as IQ-N-glucuronide, while the major metabolites included N-OH-IQ-N-glucuronide, 5-OH-IQ glucuronide and sulfate, and IQ sulfamate. The sulfate esters and sulfamates yielded 5-OH-IQ and high levels of IQ upon hydrolysis by 0.1N HCl for 15 minutes at 100°C. The 5-OH-IQ was not visualized on the HPLC chromatogram since it is a chelating agent (Cancer Letters, 51: 79, 1990). HPLC performed after acid treatment showed IQ-N-glucuronide, N-OH-IQ-N-glucuronide, 5-OH-IQ-glucuronide, and IQ. The rats drinking tea displayed a significantly higher (P < 0.05) excretion of the two major glucuronides. The above glucuronidation reactions were effected by the UGT1 gene complex of UDP-glucuronosyltransferases (UDP-GTs), induced by tea. The structures of metabolites were established by mobility on the HPLC and confirmed by electron spray mass spectrometry. We conclude that intake of green tea generally influences the manner in which the food carcinogen (IQ) is metabolized, and particularly increases the excretion of major glucuronides including N-OH-IQ-N-glucuronide, a detoxified metabolite of the proximate carcinogen N-OH-IQ, thereby most likely reducing DNA adduct formation and carcinogenesis by this class of hazardous chemicals in the human food chain.