Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochromes P450 are a large group of membrane-associated heme protein monooxygenases, most of which are responsible for metabolizing foreign compounds. Chemical carcinogens, which are ingested or absorbed into the body as inert forms, are metabolically activated by P450s to electrophilic metabolites capable of binding to and mutating DNA. Different P450 forms are responsible for activation of the various classes of chemical carcinogens including the arylamines, polycyclic aromatic hydrocarbons, nitrosamines and aflatoxins. Thus, the cellular constituency and levels of P450s could determine the fate of a particular carcinogen and the risk of humans to exposure. To study the catalytic activities of human P450s, human P450 cDNAs were cloned and expressed into active enzymes using cultured cells. By both transient and stable cDNA expression systems, several human P450s were found to be capable of metabolically-activating the human hepatocarcinogen aflatoxin B1. These cDNA expression systems can also be used to determine whether an unknown chemical will be activated by a human P450 and thus be toxic or mutagenic in humans. To assess the extent of interindividual variation in P450 expression, probes developed from P450 cDNAs are being used to quantify levels of P450 mRNAs in various human tissues. Studies using RNase protection revealed that the closely related CYP2B6 and CYP2B7 mRNAs could be independently quantified in liver and lung, respectively. This procedure can be used to examine expression of different P450 genes in banks of human tissue specimens.
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PMID:Analysis of human cytochrome P450 catalytic activities and expression. 130 34

Cytochrome P450 (CYP) enzymes expressed in human lung can metabolize a variety of xenobiotics, drugs, and endogenous compounds. Metabolism of these substrates may lead to their detoxification or activation and may affect the homeostasis of the lung, its susceptibility to disease, response to therapy, and clinical prognosis. We analyzed the expression of CYP2B7, CYP4B1, and NADPH-cytochrome P450 oxidoreductase (OR) mRNAs in normal lung controls, normal lung from lung cancer patients, and lung tumors using the sensitive technique of RNase protection. The mRNAs of CYP2B7, CYP4B1, and OR were detected in all the normal and a majority of neoplastic tissues. The three mRNAs were quantified and found at an average ratio of 0.89, 4.03, and 0.88% relative to actin mRNA in normal lung, respectively. There was no correlation between the levels of expression of the three mRNAs and the histological diagnosis of tumors. The amounts of each of the three mRNAs varied considerably between patients, but analysis of frequency distribution of the levels of CYP2B7 and CYP4B1 mRNAs did not present evidence for genetic polymorphism as a possible source of the observed interindividual variability. Levels of expression of the two P450 mRNAs were reduced (2.3- and 2.4-fold) in the neoplasms compared to normal lung. The level of OR mRNA expression was uniform with no significant differences between normal and neoplastic tissues, and its interindividual variability was the lowest amongst the three mRNAs studied. All mRNAs had increased interindividual variability in neoplastic tissues. Analysis of the patients' smoking histories and the level of CYP2B7, CYP4B1, and OR mRNAs revealed no evidence for their induction by compounds present in cigarette smoke. This study identifies and characterizes lung and lung tumor mRNAs encoding enzymes that may participate in the metabolism of xenobiotics in humans.
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PMID:Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors. 831 65