Beagle dogs are commonly used for toxicological and pharmacological studies of drug candidates in the pharmaceutical industry. Recently, we reported a CYP1A2-deficient dog with a nonsense mutation (C1117T). In this study, using CYP1A2-deficient and wild-type dog liver microsomes, substrate specificity of dog CYP1A2 was investigated and compared with human CYP1A2. For this purpose, 11 cytochrome...

CYP1A2 polymorphism has been well studied in white persons and Asians but not in Africans. We performed CYP1A2 genotype and phenotype analysis using caffeine in Ethiopians living in Ethiopia (n = 100) or in Sweden (n = 73). We sequenced the CYP1A2 gene using genomic DNA from 12 subjects, which revealed a novel intron 1 single-nucleotide polymorphism (SNP), -730C>T. We developed SNP-specific pol...

Individual differences in drug metabolism contribute to interindividual variation that characterizes responses to drugs and risk in exposure to foreign chemicals. Large individual differences are found in expression levels of CYP1A2, a major drug-metabolizing enzyme. Underlying causes for this variation are not well understood. Several factors, including tobacco smoking, consumption of crucifer...

The objective of this study was to evaluate the genotype and allelic frequencies of CYP1A2 in Chinese patients with acute liver injury induced by Polygonum multiflorum. We examined the clinical mechanism of acute liver injury induced by P. multiflorum. According to the diagnostic criteria for drug-induced liver injury (DILI), 43 cases of P. multiflorum-induced liver injury admitted to the First...

The aim of the present study was to estimate the inhibitory effect of perazine, a phenothiazine neuroleptic with piperazine structure in a side chain, on human CYP1A2 activity measured as a rate of caffeine 3-N- and 1-N-demethylation. Moreover, the influence of perazine on other caffeine metabolic pathways such as 7-N-demethylation (CYP1A2, CYP2C8/9, CYP3A4) and 8-hydroxylation (CYP3A4, CYP1A2,...

Aromatic hydrocarbon (AH) effects are mediated by binding of the AH receptor and its heterodimeric partner aromatic hydrocarbon nuclear translocator to specific response elements on DNA (AHREs). CYP1A2 expression is induced by AHs, yet AHREs have been identified in CYP1A2 genes of only two species and their functional role assessed only in the human gene. There have been few analyses of CYP1A2 ...

In vitro nuclear run-on transcription analysis using probes directed against different regions of CYP1A2 revealed that the 70-100-fold induction of CYP1A2 mRNA by polycyclic aromatic compounds is associated with a corresponding increase in the transcriptional activation of this gene in rat liver. Probes from regions of the 1st, 2nd, and 4th introns detected approximately 50-100-fold higher CYP1...

The heme containing cytochrome P450 (CYP450) enzymes participate in the phase I metabolism of drugs and other xenobiotics as well as endogenous substrates. CYP1A2 is one of the major CYP450 enzymes and account for about 13% of the total CYP450 content in the liver and is responsible for the metabolism of several clinically used drugs, e.g clozapine, olanzapine and theophylline. Even though the ...

Porphyria cutanea tarda is associated with excess hepatic production of uroporphyrin. Oxidation of uroporphyrinogen to uroporphyrin was previously demonstrated to be specifically catalyzed by cytochrome P450 (CYP) 1A2. Here, we investigated the ability of human CYP1A2 to catalyze uroporphyrinogen oxidation (UROX). UROX activity in human liver microsomes was maximally only 10% of the activity in...

This study determined the cytochrome P450 (P450) isoforms responsible for metabolism of isoflavones using human liver microsomes (HLM) and expressed P450s. The primary metabolite of genistein is 3'-OH-genistein, as identified with an authentic chemically synthesized standard. CYP1A2 was predominantly responsible for 3'-OH-genistein formation since its formation was inhibited (>50%, p < 0.05) by...