Breast Tissue Dosimetry of PhIP (2-amino-1-methyl-6 phenylimidazo 4, 5B pryidine) at Human-Relevant Exposures

摘要

The purpose of this research project is to assess if PhIP exposure at dietary levels presents a human breast cancer risk. During the period July 13, 1994 - September 30, 1998 we have studied the pharmacokinetics of PhIP following acute oral and chronic administrations at dietary-relevant doses. We have shown that PhIP is bioavailable to the breast and forms DNA adducts in this tissue following oral administrations. PhIP also forms adducts with the blood proteins albumin and hemoglobin. We have been able to demonstrate dose-response trends for tissue concentrations and adduct levels of PhIP in liver, colon and breast tissue in both male and female F344 rats, indicating that even at low dose, PhIP exposure may present a cancer risk. In chronic studies we have shown that PhIP accumulates in the tissues and that excretion occurs mainly through the feces. In lactating rats we have shown that PhIP is passed from the milk to suckling pups and may pose a carcinogenic risk to the pups. We have established that the majority of DNA adducts formed are with deoxyguanosine and the major adduct is dG-C8 PhIP. Furthermore, we have produced antibodies against PhIP-DNA and have developed a fluoroimmunoassy to detect and quantify PhIP-DNA adducts for use in molecular epidemiology studies. This work was performed under the auspices of the U.S. Department of Energy under contract W-7405-ENG-48.