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-dimethylimida zo[4,5-f] quinoxaline (MeIQx), are metabolically activated by cytochro me P4501A2 (CYP1A2) and N-acetyltransferase (NAT2), We examined the re lationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects, The subjects ate a control led diet for 7 days containing lean ground beef cooked at low temperat ure. On day 8, they were tested for CYP1A2, and NAT2 activity by caffe ine phenotyping, On the evening of day 8, subjects consumed lean groun d 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 sample s were collected and MeIQx was measured by gas chromatography-mass spe ctrometry, Using linear regression analyses, we found that higher CYP1 A2 activity was associated with lower levels of total unconjugated MeI Qx in the urine (P = 0.008) when adjusted for amount of meat eaten, wh ile NAT2 activity showed no relationship with the latter, This suggest s that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher, This findi ng supports the concept that interindividual variation in CYP1A2 activ ity may be relevant for cancers associated with exposure to HAAs.