Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4, 5-b) pyridine (PhIP)
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Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4, 5-b) pyridine (PhIP). / Frandsen, Henrik; Rasmussen, Eva S; Nielsen, Preben A; Farmer, Peter; Dragsted, Lars Ove; Larsen, John Christian.
In: Mutagenesis, Vol. 6, No. 1, 1991, p. 93-98.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4, 5-b) pyridine (PhIP)
AU - Frandsen, Henrik
AU - Rasmussen, Eva S
AU - Nielsen, Preben A
AU - Farmer, Peter
AU - Dragsted, Lars Ove
AU - Larsen, John Christian
N1 - (Ekstern)
PY - 1991
Y1 - 1991
N2 - Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-l-methyl-6-phenylimidazo(4, 5-b>)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy-amino-l-methyl-6-phenylimidazo(4, 5-b)pyridine (N-OH-PhIP). This identification was based on mass spectral (MS), UV and HPLC data by comparison with N-OH-PhIP prepared by chemical synthesis, as well as the specific activity of the compound in the Ames Salmonella test. Synthetic N-OH-PhIP was prepared by catalytic reduction of the nitro derivative of PhIP, which was synthesized from PhIP by diazotization and reaction with sodium nitrite. N-OH-PhIP was mutagenic to Salmonella typhimurium TA98 without metabolic activation and had a specific mutagenic activity of 2700 revertants/nmol. N-OH-PhIP thus seems to be a proximate mutagenic metabolite of PhIP. Other direct acting mutagens were not detected in the microsomal incubation mixture after HPLC separation. N-OH-PhIP also induced sister chromatid exchange (SCE) in Chinese hamster ovary cells (CHO cells) without metabolic activation. The specific activity of N-OH-PhIP in this assay was ∼ 3 times higher than the activity of PhIP with microsomal activation.
AB - Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-l-methyl-6-phenylimidazo(4, 5-b>)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy-amino-l-methyl-6-phenylimidazo(4, 5-b)pyridine (N-OH-PhIP). This identification was based on mass spectral (MS), UV and HPLC data by comparison with N-OH-PhIP prepared by chemical synthesis, as well as the specific activity of the compound in the Ames Salmonella test. Synthetic N-OH-PhIP was prepared by catalytic reduction of the nitro derivative of PhIP, which was synthesized from PhIP by diazotization and reaction with sodium nitrite. N-OH-PhIP was mutagenic to Salmonella typhimurium TA98 without metabolic activation and had a specific mutagenic activity of 2700 revertants/nmol. N-OH-PhIP thus seems to be a proximate mutagenic metabolite of PhIP. Other direct acting mutagens were not detected in the microsomal incubation mixture after HPLC separation. N-OH-PhIP also induced sister chromatid exchange (SCE) in Chinese hamster ovary cells (CHO cells) without metabolic activation. The specific activity of N-OH-PhIP in this assay was ∼ 3 times higher than the activity of PhIP with microsomal activation.
UR - http://www.scopus.com/inward/record.url?scp=0026080671&partnerID=8YFLogxK
U2 - 10.1093/mutage/6.1.93
DO - 10.1093/mutage/6.1.93
M3 - Journal article
C2 - 1903830
AN - SCOPUS:0026080671
VL - 6
SP - 93
EP - 98
JO - Mutagenesis
JF - Mutagenesis
SN - 0267-8357
IS - 1
ER -
ID: 254780124