Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes

Ken W Turteltaub, M. G. Knize, M. H. Buonarati, M. E. McManus, M. E. Veronese, J. A. Mazrimas, J. S. Felton

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The cytochrome P450-dependent metabolism of the heterocyclic amine mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) has been determined. We investigated the in vitro metabolism of PhIP by polycyclic hydrocarbon-induced mouse and rabbit liver microsomes, and by purified rabbit liver P450 isozymes. Following a 60 min incubation, 3-methylcholanthrene-induced mouse microsomes converted 36% of the PhIP to two major metabolites, N-hydroxy-PhIP and 4′-hydroxy-PhIP, with 43% total metabolism. Rabbit P450 form 6 and form 4 produced the same two major metabolites (20 and 5% total metabolism respectively). Additional metabolites were produced in low yields and amounts varied depending on the isozyme used (1-5%). Metabolites were not detected in incubations of PhIP with P450 forms 2 and 3C. N-Hydroxy-PhIP was found to be directly mutagenic to Salmonella TA98, while the 4′-hydroxy-PhIP was not mutagenic either with or without additional metabolic activation. These data suggest that the cytochrome P450IA isozymes are involved in the metabolism of PhIP by rabbit liver and that formation of N-hydroxy-PhIP is involved in the mutagenicity of PhIP.

Original languageEnglish (US)
Pages (from-to)941-946
Number of pages6
JournalCarcinogenesis
Volume11
Issue number6
StatePublished - Jun 1990
Externally publishedYes

Fingerprint

Liver Microsomes
Rabbit
Metabolism
Liver
Pyridine
Cytochrome P-450 Enzyme System
Isoenzymes
Metabolites
Rabbits
Mouse
Mutagens
Salmonella
Hydrocarbons
Activation
Amines
Chemical activation
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Cyclic Hydrocarbons
Proteins
Dependent

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Turteltaub, K. W., Knize, M. G., Buonarati, M. H., McManus, M. E., Veronese, M. E., Mazrimas, J. A., & Felton, J. S. (1990). Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes. Carcinogenesis, 11(6), 941-946.

Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes. / Turteltaub, Ken W; Knize, M. G.; Buonarati, M. H.; McManus, M. E.; Veronese, M. E.; Mazrimas, J. A.; Felton, J. S.

In: Carcinogenesis, Vol. 11, No. 6, 06.1990, p. 941-946.

Research output: Contribution to journalArticle

Turteltaub, KW, Knize, MG, Buonarati, MH, McManus, ME, Veronese, ME, Mazrimas, JA & Felton, JS 1990, 'Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes', Carcinogenesis, vol. 11, no. 6, pp. 941-946.
Turteltaub, Ken W ; Knize, M. G. ; Buonarati, M. H. ; McManus, M. E. ; Veronese, M. E. ; Mazrimas, J. A. ; Felton, J. S. / Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes. In: Carcinogenesis. 1990 ; Vol. 11, No. 6. pp. 941-946.
@article{4ec370eae54947e9b4adb4336d339e3f,
title = "Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes",
abstract = "The cytochrome P450-dependent metabolism of the heterocyclic amine mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) has been determined. We investigated the in vitro metabolism of PhIP by polycyclic hydrocarbon-induced mouse and rabbit liver microsomes, and by purified rabbit liver P450 isozymes. Following a 60 min incubation, 3-methylcholanthrene-induced mouse microsomes converted 36{\%} of the PhIP to two major metabolites, N-hydroxy-PhIP and 4′-hydroxy-PhIP, with 43{\%} total metabolism. Rabbit P450 form 6 and form 4 produced the same two major metabolites (20 and 5{\%} total metabolism respectively). Additional metabolites were produced in low yields and amounts varied depending on the isozyme used (1-5{\%}). Metabolites were not detected in incubations of PhIP with P450 forms 2 and 3C. N-Hydroxy-PhIP was found to be directly mutagenic to Salmonella TA98, while the 4′-hydroxy-PhIP was not mutagenic either with or without additional metabolic activation. These data suggest that the cytochrome P450IA isozymes are involved in the metabolism of PhIP by rabbit liver and that formation of N-hydroxy-PhIP is involved in the mutagenicity of PhIP.",
author = "Turteltaub, {Ken W} and Knize, {M. G.} and Buonarati, {M. H.} and McManus, {M. E.} and Veronese, {M. E.} and Mazrimas, {J. A.} and Felton, {J. S.}",
year = "1990",
month = "6",
language = "English (US)",
volume = "11",
pages = "941--946",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) by liver microsomes and isolated rabbit cytochrome P450 isozymes

AU - Turteltaub, Ken W

AU - Knize, M. G.

AU - Buonarati, M. H.

AU - McManus, M. E.

AU - Veronese, M. E.

AU - Mazrimas, J. A.

AU - Felton, J. S.

PY - 1990/6

Y1 - 1990/6

N2 - The cytochrome P450-dependent metabolism of the heterocyclic amine mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) has been determined. We investigated the in vitro metabolism of PhIP by polycyclic hydrocarbon-induced mouse and rabbit liver microsomes, and by purified rabbit liver P450 isozymes. Following a 60 min incubation, 3-methylcholanthrene-induced mouse microsomes converted 36% of the PhIP to two major metabolites, N-hydroxy-PhIP and 4′-hydroxy-PhIP, with 43% total metabolism. Rabbit P450 form 6 and form 4 produced the same two major metabolites (20 and 5% total metabolism respectively). Additional metabolites were produced in low yields and amounts varied depending on the isozyme used (1-5%). Metabolites were not detected in incubations of PhIP with P450 forms 2 and 3C. N-Hydroxy-PhIP was found to be directly mutagenic to Salmonella TA98, while the 4′-hydroxy-PhIP was not mutagenic either with or without additional metabolic activation. These data suggest that the cytochrome P450IA isozymes are involved in the metabolism of PhIP by rabbit liver and that formation of N-hydroxy-PhIP is involved in the mutagenicity of PhIP.

AB - The cytochrome P450-dependent metabolism of the heterocyclic amine mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) has been determined. We investigated the in vitro metabolism of PhIP by polycyclic hydrocarbon-induced mouse and rabbit liver microsomes, and by purified rabbit liver P450 isozymes. Following a 60 min incubation, 3-methylcholanthrene-induced mouse microsomes converted 36% of the PhIP to two major metabolites, N-hydroxy-PhIP and 4′-hydroxy-PhIP, with 43% total metabolism. Rabbit P450 form 6 and form 4 produced the same two major metabolites (20 and 5% total metabolism respectively). Additional metabolites were produced in low yields and amounts varied depending on the isozyme used (1-5%). Metabolites were not detected in incubations of PhIP with P450 forms 2 and 3C. N-Hydroxy-PhIP was found to be directly mutagenic to Salmonella TA98, while the 4′-hydroxy-PhIP was not mutagenic either with or without additional metabolic activation. These data suggest that the cytochrome P450IA isozymes are involved in the metabolism of PhIP by rabbit liver and that formation of N-hydroxy-PhIP is involved in the mutagenicity of PhIP.

UR - http://www.scopus.com/inward/record.url?scp=0025324196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025324196&partnerID=8YFLogxK

M3 - Article

C2 - 2347068

AN - SCOPUS:0025324196

VL - 11

SP - 941

EP - 946

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -