TY - JOUR
T1 - Activation and effects of the food-derived heterocyclic amines in extrahepatic tissues.
AU - Overvik, E.
AU - Hellmold, H.
AU - Branting, C.
AU - Gustafsson, J. A.
N1 - Funding Information:
This research received funding from the Deutsche Forschungsgemeinschaft (Germany) within the project LA/1416/9-1 and from the Max-Buchner-Forschungsstiftung (Germany). Financial support from Johan Gadolin Process Chemistry Centre, ?bo Akademi University (Finland), is gratefully acknowledged.
Copyright:
This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PY - 1995
Y1 - 1995
N2 - Humans frequently inhale as well as ingest cooked-food mutagens, among which the heterocyclic amines are the quantitatively most important. An extensive systemic distribution of these mutagens implies that most tissues in the body are exposed. Tissues containing cytochrome P450 (CYP) may be particularly susceptible to DNA damage. Accordingly, animal experiments have shown that oral exposure to heterocyclic amines leads to tumor formation at multiple sites. CYP1A2, which has only been demonstrated in the liver, seems to be the isozyme most efficient in metabolically activating the heterocyclic amines. In extrahepatic tissues, however, other CYP forms are likely to be important. Using Salmonella mutagenicity as an endpoint, we have studied the metabolic activation of 2-amino-3-methylimidazo[4,5,f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5,f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by isolated lung microsomes from rats and mice. Our studies show that CYP2A3, an isozyme that has hitherto not been investigated with regard to its capacity to activate heterocyclic amines, catalyses a major part of the IQ activating reactions in the uninduced lung. The formation of mutagens during cooking of meat is highly temperature dependent and meat extracts heated at 200 degrees C show a strong mutagenic activity in the Ames Salmonella assay. These extracts caused mutations at the HPRT locus in normal human fibroblasts as well as a pronounced decrease in survival of the cells. Furthermore, the heated meat extracts caused a decreased proliferative activity in primary cultures of normal mouse colonic epithelial cells as measured by autoradiography.
AB - Humans frequently inhale as well as ingest cooked-food mutagens, among which the heterocyclic amines are the quantitatively most important. An extensive systemic distribution of these mutagens implies that most tissues in the body are exposed. Tissues containing cytochrome P450 (CYP) may be particularly susceptible to DNA damage. Accordingly, animal experiments have shown that oral exposure to heterocyclic amines leads to tumor formation at multiple sites. CYP1A2, which has only been demonstrated in the liver, seems to be the isozyme most efficient in metabolically activating the heterocyclic amines. In extrahepatic tissues, however, other CYP forms are likely to be important. Using Salmonella mutagenicity as an endpoint, we have studied the metabolic activation of 2-amino-3-methylimidazo[4,5,f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5,f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by isolated lung microsomes from rats and mice. Our studies show that CYP2A3, an isozyme that has hitherto not been investigated with regard to its capacity to activate heterocyclic amines, catalyses a major part of the IQ activating reactions in the uninduced lung. The formation of mutagens during cooking of meat is highly temperature dependent and meat extracts heated at 200 degrees C show a strong mutagenic activity in the Ames Salmonella assay. These extracts caused mutations at the HPRT locus in normal human fibroblasts as well as a pronounced decrease in survival of the cells. Furthermore, the heated meat extracts caused a decreased proliferative activity in primary cultures of normal mouse colonic epithelial cells as measured by autoradiography.
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M3 - Review article
C2 - 8844803
AN - SCOPUS:0029422212
VL - 23
SP - 123
EP - 133
JO - Princess Takamatsu symposia
JF - Princess Takamatsu symposia
ER -