Chapter title |
Chemical methods for assessing systemic exposure to dietary heterocyclic amines in man.
|
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Chapter number | 25 |
Book title |
Toxicology - From Cells to Man
|
Published in |
Archives of toxicology Supplement Archiv für Toxikologie Supplement, January 1996
|
DOI | 10.1007/978-3-642-61105-6_25 |
Pubmed ID | |
Book ISBNs |
978-3-64-264696-6, 978-3-64-261105-6
|
Authors |
Donald S. Davies, Nigel J. Gooderham, Stephen Murray, Anthony Lynch, Rafael de la Torre, Jorge Segura, Allan R. Boobis, Davies, Donald S., Gooderham, Nigel J., Murray, Stephen, Lynch, Anthony, Torre, Rafael de la, Segura, Jorge, Boobis, Allan R., de la Torre, Rafael, Torre, Rafael |
Abstract |
A significant proportion of the mutagenic material present in cooked beef is accounted for by 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which are formed during the cooking of meat. N-hydroxylation catalyzed by CYP1A2 is the major pathway of metbolism of MeIQx and PhIP and is solely responsible for the generation of mutagenic species. Assays for MeIQx and PhIP in foods and body fluids were developed utilising gas chromatography/mass spectrometry with stable isotope labelled analogues as internal standards. Studies using these assays have demonstrated that both MeIQx and PhIP are well absorbed and extensively metabolised following ingestion of amine-containing beef by humans. Studies in which furafylline, a potent and selective inhibitor of human CYP1A2, was administered before ingestion of beef revealed that more than 90% of MeIQx and 70% of PhIP are N-hydroxylated in vivo, probably pre-systemically in the liver. The results demonstrate that unchanged MeIQx and PhIP in urine are accurate and sensitive measures of systemic exposure to the amines. |
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