LOWER LEVELS OF URINARY 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE (MEIQX) IN HUMANS WITH HIGHER CYP1A2 ACTIVITY

Heterocyclic aromatic amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2), We examined the relationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects, The subjects ate a controlled diet for 7 days containing lean ground beef cooked at low temperature. On day 8, they were tested for CYP1A2, and NAT2 activity by caffeine phenotyping, On the evening of day 8, subjects consumed lean ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected and MeIQx was measured by gas chromatography-mass spectrometry, Using linear regression analyses, we found that higher CYP1A2 activity was associated with lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted for amount of meat eaten, while NAT2 activity showed no relationship with the latter, This suggests that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher, This finding supports the concept that interindividual variation in CYP1A2 activity may be relevant for cancers associated with exposure to HAAs.