F. Peter Guengerich

Kinetics of Nucleotide Incorporation Opposite DNA Bulky Guanine (2008)

Hong Zang, Thomas M. Harris, F. Peter Guengerich

Six oligonucleotides with carcinogen derivatives bound at the N2 atom of deoxyguanosine were prepared, including adducts derived from butadiene, acrolein, crotonaldehyde, and styrene, and examined...

Mapping the Genetic Architecture of Gene Expression in Human Liver (2008)

Eric E. Schadt, Cliona Molony, Eugene Chudin, Ke Hao, Xia Yang, Pek Y. Lum, ...

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order...

Activation of aminophenylnorharman, aminomethylphenylnorharman and aminophenylharman to genotoxic metabolites by human N-acetyltransferases and cytochrome P450 enzymes expressed in Salmonella typhimurium umu tester strains (2006)

Oda, Yoshimitsu, Totsuka, Yukari, Wakabayashi, Keiji, Guengerich, F.Peter, Shimada, Tsutomu

Norharman (9H-pyrido[3,4-b]indole) and harman (1-methyl-9H-pyrido[3,4-b]indole) contained in cigarette smoke and cooked foodstuffs, are non-mutagenic to Salmonella strains, but show co-mutagenicity...

Activation of aminophenylnorharman, aminomethylphenylnorharman and aminophenylharman to genotoxic metabolites by human N-acetyltransferases and cytochrome P450 enzymes expressed in Salmonella typhimurium umu tester strains (2006)

Oda, Yoshimitsu, Totsuka, Yukari, Wakabayashi, Keiji, Guengerich, F. Peter, Shimada, Tsutomu

Norharman (9H-pyrido[3,4-b]indole) and harman (1-methyl-9H-pyrido[3,4-b]indole) contained in cigarette smoke and cooked foodstuffs, are non-mutagenic to Salmonella strains, but show co-mutagenicity...

Role of glutamic acid 216 in cytochrome P450 2D6 substrate binding and catalysis (2003)

Guengerich, F. Peter, Hanna, Imad H., Martin, Martha V., Gillam, Elizabeth M. J.

Human cytochrome P450 (P450) 2D6 is an important enzyme involved in the metabolism of drugs, many of which are amines or contain other basic nitrogen atoms. Asp301 has generally been considered to be...

Role of glutamic acid 216 in cytochrome P450 2D6 substrate binding and catalysis (2003)

Guengerich, F. Peter, Hanna, Imad H., Martin, Martha V., Gillam, Elizabeth M. J.

Human cytochrome P450 (P450) 2D6 is an important enzyme involved in the metabolism of drugs, many of which are amines or contain other basic nitrogen atoms. Asp301 has generally been considered to be...

Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs (2001)

Soucek, Pavel, Zuber, Roman, Anzenbacherová, Eva, Anzenbacher, Pavel, Guengerich, F Peter

Abstract Background The search for an optimal experimental model in pharmacology is recently focused on (mini)pigs as they seem not only to be an alternative source of cells and tissues for...

The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines (2001)

Yueh, Mei-Fei, Nguyen, Nghia, Famourzadeh, Maryam, Strassburg, Christian P., Oda, Yoshimitsu, Guengerich, F.Peter, ...

The importance of environmental and dietary arylamines, and heterocyclic amines in the etiology of human cancer is of growing interest. These pre-carcinogens are known to undergo bioactivation by...

Formation and metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol enantiomers in vitro in mouse, rat and human tissues (2000)

Upadhyaya, Pramod, Carmella, Steven G., Guengerich, F.Peter, Hecht, Stephen S.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a major metabolite of the tobacco-specific lung carcino- gen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNAL has a chiral center at...

Metabolism of chemical carcinogens (2000)

Guengerich, F. Peter

The transformation of chemicals is important in carcinogenesis, both in bioactivation and detoxification. Major advances in the past 20 years include appreciation of the migration of reactive...

Catalytic properties of polymorphic human cytochrome P450 1B1 variants (1999)

Shimada, Tsutomu, Watanabe, Junko, Kawajiri, Kaname, Sutter, Thomas R., Guengerich, F. Peter, Gillam, Elizabeth M.J., ...

Four polymorphic human cytochrome P450 (CYP) 1B1 allelic variants, namely Arg48,Ala119,Leu432,Asn453, Arg48,Ser119,Leu432,Asn453, Arg48,Ala119,Val432,Asn-453 and Arg48,Ser119,Val432,Asn453, were...

Drug Metabolic Enzymes in Developmental Toxicology (1996)

MILLER, MARK STEVEN, JUCHAU, MONT R., GUENGERICH, F. PETER, NEBERT, DANIEL W., RAUCY, JUDY L.

Although much is known about the metabolism of environmental toxicants in adult organisms, little information exists on the role of cytochrome P450 (CYP) enzymes during development. The developing...

SHORT COMMUNICATION: Human glutathione S-transferase T1-1 enhances mutagenicity of 1, 2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium (1996)

Thier, Ricarda, Pemble, Sally E., Kramer, Harry, Taylor, John B., Guengerich, F.Peter, Ketterer, Brian

The rat theta class glutathione S-transferase (GST) 5–5 has been shown to affect the mutagenicity of halogenated alkanes and epoxides. In Salmonella typhimurium TA1535 expressing the rat GST5–5...

A new Salmonella typhimurium NM5004 strain expressing rat glutathione S-transferase 5-5: use in detection of genotoxicity of dihaloalkanes using an SOS/umu test system (1996)

Oda, Yoshimitsu, Yamazaki, Hiroshi, Thier, Ricarda, Ketterer, Brian, Guengerich, F.Peter, Shimada, Tsutomu

The Escherichia coli mu operon was subcloned into a pKK233–2 vector containing rat glutathione S-transferase (GST) 5–5 cDNA and the plasmid thus obtained was introduced into Salmonella...

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate (1996)

Smith, Theresa J., Guo, Zuyu, Guengerich, F.Peter, Yang, Chung S.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific nitrosamine in animals and has been suggested to play a role in human tobacco-related cancers. Our previous study...

Non-specific inhibition of cytochrome P450 activities by chlorophyllin in human and rat liver microsomes (1995)

Yun, Chul-Ho, Jeong, Hye Gwang, Jhoun, Jay Woo, Guengerich, F.Peter

Chlorophyllin, a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, inhibits the mutagenicity of 2-amino-3-methylimidazo[4, 5-f)quinoline (IQ),...

Procarcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes (1995)

Yamazaki, Hiroshi, Inui, Yukiharu, Wrighton, Steven A., Guengerich, F.Peter, Shimada, Tsutomu

Recent studies indicate that cytochrome P450 (P450) 3A4 plays important roles in the activation of procarcinogens such as aflatoxin B1 and sterigmatocystin, as well as in the oxidation of a number of...

Activation of trans-l,2-dihydro-l,2-dihydroxy-6-aminochrysene to genotoxic metabolites by rat and human cytochromes P450 (1994)

Yamazaki, Hiroshi, Mimura, Mayumi, Oda, Yoshimitsu, Gonzalez, Frank J., El-Bayoumy, Karam, Chae, Young-Heum, ...

In order to address the hypothesis that 6-aminochrysene (6-AC) is converted to genotoxic products by cytochrome P450 enzymes via two activation pathways (N-hydroxylation and epoxidation), the...

Activation of procarcinogens by human cytochrome P450 enzymes expressed in Escherichia coli. Simplified bacterial systems for genotoxicity assays (1994)

Shimada, Tsutomu, Gillam, Elizabeth M.J., Sandhu, Punam, Guo, Zuyu, Tukey, Robert H., Guengerich, F.Peter

Bacterial assays were used to examine the activation of 14 known procarcinogens by cytochrome P450 (P450) enzymest†. Human P450s 1A1, 1A2 and 3A4 were expressed in Escherichia coil with slight...

Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice (1993)

Csanády, György, Guengerich, F. Peter, Bond, James A.

In Table VI of the above paper, the values for Cytosolic glutathione S-transferase should be: mouse, 4.36; rat, 5.66; and human, 0.47. This change results in overall activation/detoxification ratios...

Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice (1992)

Csanády, György A., Guengerich, F.Peter, Bond, James A.

1,3-Butadiene (BD), a widely used monomer in the production of synthetic rubber and other resins, is one of the 189 hazardous air pollutants identified in the 1990 Clean Air Act Amendments. BD...

Contributions of human liver cytochrome P450 enzymes to the N-oxidation of 4,4'-methylene-bis(2-chloroaniline) (1992)

Yun, Chul-Ho, Shimada, Tstuomu, Guengerich, F.Peter

4,4′-Methylene-bis(2-chloroaniline) (MOCA) can produce tumors in rodents and dogs and an increased incidence of bladder tumors has been reported in exposed workers. It is therefore of interest to...

Participation of rat liver cytochrome P450 2E1 in the activation of N-nitrosodimethylamine and N-nitrosodiethylainine to products genotoxic in an acetyltransferase-overexpressing Salmonella typhimurium strain (NM2009) (1992)

Yamazaki, Hiroshi, Oda, Yoshimitsu, Funae, Yoshihiko, Imaoka, Susumu, Inui, Yukiharu, Guengerich, F.Peter, ...

The possible roles of cytochrome P450 (P450) enzymes in the metabolic activation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) by rat liver microsomes have been examined in a...

Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes (1992)

Yamazaki, Hiroshi, Inui, Yukiharu, Yun, Chul-Ho, Guengerich, F.Peter, Shimada, Tsutomu

An acetyltransferase-overexpressing strain of Salmonella typhimurium (NM2009) has been used to investigate roles of human liver microsomal cytochrome P450 (P450) enzymes in the activation of...

Roles of different cytochrome P450 enzymes in bioactivation of the potent hepatocarcinogen 3-methoxy-4-aminoazobenzene by rat and human liver microsomes (1991)

Yamazaki, Hiroshi, Degawa, Masakuni, Funae, Yoshihiko, Imaoka, Susumu, Inui, Yukiharu, Guengerich, F.Peter, ...

The potent hepatocarcinogen 3-methoxy-4-aminoazobenzene (3-MeO-AAB) has been reported to be bioactivated to mutagenic intermediates by rat liver microsomal cytochrome P450 (P450) and to be a...

Role of cytochrome P450IIIA4 in the metabolism of the pyrrolizidine alkaloid senecionine in human liver (1991)

Miranda, Cristobal L., Reed, Ralph L., Guengerich, F. Peter, Buhler, Donald R.

Studies were carried out to investigate the metabolism of senecionine by human liver microsomes and the role of human cytochrome P450IIIA4 in this process. Human liver microsomes metabolized...

Metabolic deactivation of furylfuramide by cytothrome P450 in human and liver microsomes (1990)

Shimada, Tsutomu, Yamazaki, Hiroshi, Shimura, Hisashi, Tanaka, Ryo-ichi, Guengerich, F.Peter

Metabolic deactivation of furylfuramide by human and rat liver microsomal cytochrome P450 enzymes has been investigated in a system measuring induction of umu gene expression response in Salmonella...

Formation of the DNA adduct S-[2-(N7-guanyl)ethyl]glutathione from ethylene dibromide: effects of modulation of glutathione and glutathione S-transferase levels and lack of a role for sulfation (1990)

Kim, Dong-Hyun, Guengerich, F.Peter

Hepatic S-[2-(N7-guanyl)ethyl]glutathione DNA adducts were determined in several strains of rats and mice after i.p. injection of a dose of 37 mg ethylene dibromide/kg body wt. More adducts were...

Differential rates of metabolic activation and detoxication of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by different cytochrome P450 enzymes (1990)

Wallin, Håkan, Mikalsen, Arne, Guengerich, F.Peter, Ingelman-Sundberg, Magnus, Solberg, Karin E., Rossland, Ole Jørgen, ...

Rat liver microsomes metabolized the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to the genotoxic metabolite 2-hydroxamino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine...

The S-acetyl coenzyme A-dependent metabolic activation of the carcinogen N-hydroxy-2-aminofluorene by human liver cytosol and its relationship to the aromatic amine N-acetyltransferase phenotype (1987)

Flammang, Thomas J., Yamazoe, Yasushi, Guengerich, F.Peter, Kadlubar, Fred F.

A genetic polymorphism in the enzymatic N-acetylation of sulfamethazine and other drugs in humans is well known and has been related to differential susceptibility to drug toxicities. Carcinogenic...

Glutathione-mediated binding of dibromoalkanes to DNA: specificity of rat glutathione-S-transferases and dibromoalkane structure (1984)

Inskeep, Philip B., Guengerich, F.Peter

1,2-Dibromo-[1,2-14C]ethane was bound irreversibly to DNA when glutathione S-transferase or rat liver cytosolic components were added to incubations of calf thymus DNA and glutathione at 37°C. There...

Different patterns of benzo[a]pyrene metabolism of purified cytochromes P-450 from methylcholanthrene, {beta}-naphthoflavone and phenobarbital treated rats (1982)

Gozukara, Engin M., Guengerich, F. Peter, Miller, Haruko, Gelboin, Harry V.

An improved high-pressure liquid chromatography system was used to analyze the amount of benzo[a]pyrene metabolites formed in reconstituted microsomal mixed-function oxidase systems containing...

Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: Kinetic analysis of covalent binding and DNA-induced hydrolysis

Johnson, William W., Guengerich, F. Peter

The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via an SN2 reaction from an intercalated...

Cytochromes P450 are Expressed in Proliferating Cells in Barrett's Metaplasia

Hughes, Steven J, Morse, Mark A, Weghorst, Christopher M, Kim, Hyesook, Watkins, Paul B, Guengerich, F Peter, ...

The expression of cytochromes P450 (CYP) in Barrett's esophagus and esophageal squamous mucosa was investigated. Esophagectomy specimens from 23 patients were examined for CYP expression of CYP1A2,...

Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: Kinetic analysis of covalent binding and DNA-induced hydrolysis

Johnson, William W., Guengerich, F. Peter

The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via an SN2 reaction from an intercalated...

Cytochromes P450 are Expressed in Proliferating Cells in Barrett's Metaplasia

Hughes, Steven J, Morse, Mark A, Weghorst, Christopher M, Kim, Hyesook, Watkins, Paul B, Guengerich, F Peter, ...

The expression of cytochromes P450 (CYP) in Barrett's esophagus and esophageal squamous mucosa was investigated. Esophagectomy specimens from 23 patients were examined for CYP expression of CYP1A2,...

Mapping the Genetic Architecture of Gene Expression in Human Liver

Schadt, Eric E, Molony, Cliona, Chudin, Eugene, Hao, Ke, Yang, Xia, Lum, Pek Y, ...

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order...

Development of Oxidative Stress by Cytochrome P450 Induction in Rodents Is Selective for Barbiturates and Related to Loss of Pyridine Nucleotide-dependent Protective Systems*S⃞

Dostalek, Miroslav, Hardy, Klarissa D., Milne, Ginger L., Morrow, Jason D., Chen, Chi, Gonzalez, Frank J., ...

Reactive oxygen species (ROS) and oxidative stress have been considered in a variety of disease models, and cytochrome P450 (P450) enzymes have been suggested to be a source of ROS. Induction of...

Kinetic Analysis of Translesion Synthesis Opposite Bulky N2- and O6-Alkylguanine DNA Adducts by Human DNA Polymerase REV1*S⃞

Choi, Jeong-Yun, Guengerich, F. Peter

REV1, a Y family DNA polymerase (pol), is involved in replicative bypass past DNA lesions, so-called translesion DNA synthesis. In addition to a structural role as a scaffold protein, REV1 has been...

Cytochrome P450s and other enzymes in drug metabolism and toxicity

Guengerich, F. Peter

The cytochrome P450 (P450) enzymes are the major catalysts involved in the metabolism of drugs. bioavailability and toxicity are 2 of the most common barriers in drug development today, and P450 and...