The mechanisms underlying phenacetin-induced toxicity and carcinogenicity are not clear. In particular, it is not known whether these effects are mediated by metabolic activation of the drug. CYP1A2 is known to metabolize phenacetin in vitro. To determine the role of this enzyme in vivo, the toxicity and carcinogenicity of phenacetin was examined in Cyp1a2-null mice (that lack CYP1A2). Six- to ...

CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16alpha-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16alpha-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (> or =2 cups per day) combi...

BACKGROUND The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. METHODOLOGY/PRINCIPAL FINDINGS The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer s...

The aryl hydrocarbon receptor (AHR) plays a central role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) hepatotoxicity, regulation of xenobiotic metabolism, and hepatovascular development. Each of these processes appears to be dependent on binding of the AHR to dioxin- responsive elements (DREs) within the genome. The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important role...

Cytochrome P450 (CYP) enzymes are widely studied for their involvement in metabolism of drugs and endogenous compounds. In porcine liver, CYP1A2, 2A and 2E1 are important for the metabolism of skatole. Feeding chicory roots to pigs is known to decrease the skatole concentration in plasma and fat. In the present study we investigated the effect of chicory on CYP mRNA and protein expression, as w...

Pueraria candollei var. mirifica (PM) is a Thai traditional medicinal plant for rejuvenation and estrogen replacement therapy in menopausal women. CYP1A1 and CYP1A2 proteins are the members of hepatic cytochrome P450 (CYP) enzymes to activate a procarcinogen, in which ethoxyresorufin O-demethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities are the specific markers for CYP1A1 an...

5-(3-methoxyphenyl)-3-(5-methyl-1,2,4-oxadiazol-3-yl)-2-oxo-1,2-dihydro-1,6-naphthyridine (AC-3933) is a novel cognitive enhancer with central benzodiazepine receptor partial inverse agonistic activity. AC-3933 is predominantly metabolized to hydroxylated metabolite [SX-5745; 3-(5-hydroxymethyl-1,2,4-oxadiazol-3-yl)-5-(3-methoxyphenyl)-2-oxo-1,2-dihydro-1,6-naphthyridine] in dog. Initially, we ...

Flavonoids are a class of dietary phytochemicals that modulate various biological activities. The effects of flavone and five hydroxylated derivatives on the methoxyresorufin O-demethylase activity catalyzed by cDNA-expressed human cytochromes P450 (CYP)1A1 and 1A2 were examined. Flavone was a less potent inhibitor of CYP1A1 (IC50 = 0.14 microM) than CYP1A2 (IC50 = 0.066 microM). Four hydroxyla...

The cytochrome P4501A enzymes play important roles in carcinogen metabolism. We reported previously that 3-methylcholanthrene (MC) elicits a persistent induction of hepatic, pulmonary, and mammary microsomal cytochrome P450 (P450) 1A enzymes for several weeks after MC withdrawal. In this study, we tested the hypothesis that CYP1A2, a liver-specific P450 isozyme, plays an important role in the m...

Mexiletine, lidocaine, and tocainide are class IB antiarrhythmic drugs that are used for the treatment of ventricular arrhythmias and are known to inhibit drug metabolism. The objectives of this study were to characterize the inhibitory effects of mexiletine, lidocaine, and tocainide on cytochrome P-450 1A2 (CYP1A2) activity in human liver microsomes and to evaluate their relative inhibitory po...