Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene.
Epidemiological evidence has suggested an association between meat consumption and the risk of breast cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, has been implicated in the aetiology of breast cancer and has been shown to induce tumour formation in rodent mammary glands. In addition, polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) which has also been shown to induce tumour formation at a number of sites in rodents including the breast, are produced during the cooking of meat through the pyrolysis of fats. The aim of this study was to examine the bioavailability of these compounds to human breast tissue and their ability to bind to DNA to form DNA adducts. Patients undergoing breast surgery at York District Hospital were orally administered prior to surgery a capsule containing 20microg of 14C PhIP (182kBq, specific activity 2.05GBq/mmol) or 5microg of 14C B[a]P (36kBq, specific activity 1.81GBq/mmol). At surgery, normal and tumour breast tissue was resected and tissue concentrations of carcinogen measured by liquid scintillation counting and DNA adduct levels by accelerator mass spectrometry (AMS) were subsequently determined. It was found that both 14C PhIP and 14C B[a]P were able to reach the target organ where they had the ability to form DNA adducts. The level of adducts ranged from 26.22-477.35 and 6.61-208. 38 adducts/10(12) nucleotides following administration of 14C PhIP and 14C B[a]P, respectively, with no significant difference observed between levels in normal or tumour tissue. In addition, the data obtained in this study were comparable to adduct levels previously found in colon samples following administration of the same compounds to individuals undergoing colorectal surgery. This is the first report that these two carcinogens bind to human breast DNA after administration of a defined low dose.
Lightfoot
T J
TJ
JBUMC, Department of Biology, University of York, PO Box 373, YO1 5YW, York, UK. tjl4@york.ac.uk
Coxhead
J M
JM
Cupid
B C
BC
Nicholson
S
S
Garner
R C
RC
D000368:Aged; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D001940:Breast / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000493:pharmacokinetics*; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D008198:Lymph Nodes / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D010315:Particle Accelerators
D002250:Carbon Radioisotopes; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; D001564:Benzo(a)pyrene; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine