Dacarbazine (DTIC), a widely used anticancer agent, is inactive until metabolized in the liver by cytochromes P450 to form the reactive N-demethylated species 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC). The modest activity of DTIC in the treatment of cancer patients has been attributed in part to lower ...

Baicalin has been used as mainly bioactive constituent of about 100 kinds of traditional Chinese medicines in Chinese pharmacopoeia. The effect of baicalin on cytochrome P450 should be paid more attention because baicalin was used widely. The aim of this study was to investigate whether baicalin could inhibit CYP1A2 in pooled human liver microsomes (HLMs) and in rats in vivo and the gene polymo...

Here we describe a transgenic mouse model [Crl:CD-1(ICR)BR-Tg(Cyp1a2-luc)Xen] using luciferase as a reporter for Cyp1a2 gene regulation. An 8.4-kilobase mouse Cyp1a2 promoter driving the firefly luciferase gene was microinjected into single-cell-stage CD-1 mouse embryos. A transgenic mouse line was selected based on basal and induced levels of the transgene in mouse liver by an in vivo biolumin...

Although there is a putative GC box in the cytochrome P450 1A2 (CYP1A2) promoter, its function has remained undetermined. To understand the molecular mechanisms controlling CYP1A2 gene expression in the liver, we studied the roles of the GC box in promoter activity and the effects of its CpG methylation on CYP1A2 gene expression. The results of luciferase assays showed that promoter activity wa...

Numerous metabolism studies have demonstrated that the toxic contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is poorly metabolized. A hallmark feature of TCDD exposure is induction of hepatic CYP1A2 and subsequent sequestration leading to high liver-to-fat concentration ratios. This study was initiated to determine whether TCDD was inherently poorly metabolized or unavailable for metabol...

Previous studies have shown that the presence of one P450 enzyme can affect the function of another. The goal of the present study was to determine if P450 enzymes are capable of forming homomeric complexes that affect P450 function. To address this problem, the catalytic activities of several P450s were examined in reconstituted systems containing NADPH-POR (cytochrome P450 reductase) and a si...

The inhibitory effects of flavonoids on the human cytochrome P450 1A2 (CYP1A2) were examined. Among flavonoids tested, galangin, kaempferol, chrysin, and apigenin were potent inhibitors. Although apigenin belonging to flavones and genistein belonging to isoflavones are similar in the chemical structures, the inhibitory potencies for CYP1A2 were distinguished markedly between these two flavonoid...

BACKGROUND Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526, and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present meta-analysis of the literature was performed to derive a more precise estimation of the relationship. MATERIALS AND METHODS 8 publications covering 23 studies were selected for this meta-analy...

BACKGROUND Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. We recently observed that a group of type-2 diabetes patients consumed more caffeine (coffee) on a daily basis than non-type-2 diabetes controls. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. METHODS To estimate CYP1A2 enzyme...