Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human epidermoid carcinoma A431 cells, possessing an extraordinarily high number of epidermal growth factor (EGF) receptors (1), were found to be hypotetraploid in their chromosome constitution and to contain two copies of intact chromosome 7 and two types of the translocation chromosomes involving chromosome 7 (M4 and M14) as well as several other rearranged chromosomes. The A431 cells were fused with mouse A9 cells, which lack EGF receptors (2) and are deficient in hypoxanthine phosphoribosyltransferase (3), and the human-mouse cell hybrid (AA series) were selected in HAT/ouabain medium (3, 4). The expression of high EGF binding ability was correlated with the presence of human translocation chromosome M4. AA hybrid clones that contained intact human chromosome 7 but not the marker chromosome M4 expressed only ordinary levels of EGF receptors. The EGF receptors expressed in the AA hybrids were proven to be of human nature by immunoprecipitation of the receptors cross-linked with [125I]EGF. These observations and our previous gene assignment of the EGF receptor to human chromosome 7 (2, 5) suggest that the marker chromosome M4 may carry an alteration(s) in the gene(s) involved in EGF receptor biosynthesis.
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PMID:Genetic analysis of hyperproduction of epidermal growth factor receptors in human epidermoid carcinoma A431 cells. 632 59

We have developed a culture system for detecting and isolating rare hypoxanthine phosphoribosyltransferase-deficient mutants of human epidermal keratinocytes. A thioguanine-resistant variant, 3T3M1, of the Swiss mouse fibroblast line 3T3 was used as a feeder layer to support clonal growth of mutant keratinocytes. A near-diploid, epidermal squamous cell carcinoma line, SCC-13Y, was used as a prototype to determine mutagen treatment conditions, plating density, and phenotypic expression time for maximum mutant recovery. To extend this system to normal keratinocytes, we improved the culture conditions by adding insulin, adenine, and Ham's nutrient mixture F-12, which increased colony-forming efficiencies to 30% in early passage and made feasible the detection of rare mutants in normal epidermal keratinocyte populations. We have quantitated mutation in SCC-13Y and three strains of normal human epidermal keratinocytes after exposure to polycyclic aromatic hydrocarbons, which are activated to their mutagenic forms by cellular mixed-function oxidases. 7,12-Dimethylbenz[a]anthracene and benzo[a]pyrene caused almost no cytotoxicity, but induced thioguanine-resistant mutants at frequencies as much as 50-fold higher than the spontaneous frequency of approximately 10(-6). The mutants were aminopterin-sensitive and possessed no measurable hypoxanthine phosphoribosyltransferase activity; their behavior was indistinguishable from that of keratinocytes cultured from individuals with Lesch-Nyhan syndrome. This mutagenesis assay system should also be applicable to other feeder layer-dependent human epithelial cell types, such as urothelial, mammary, and tracheal epithelial cells.
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PMID:Polycyclic aromatic hydrocarbon mutagenesis of human epidermal keratinocytes in culture. 644 Jan 45

Areca quid (AQ) chewing and smoking have synergistic potential in the development of oral squamous cell carcinoma (OSCC). In Taiwan, fresh Piper betle inflorescence is uniquely added to AQ, and hydroxychavicol (HC) is the major phenolic component of P. betle inflorescence. This study investigated whether HC modulates cigarette carcinogen benzo[a]pyrene (B[a]P)-mediated toxic effects. Pretreatment of HC and followed by B[a]P challenge resulted in higher cytotoxicity and HPRT gene mutation frequency (P < 0.05). However, this treatment protocol resulted in decreased bulky B[a]P-DNA adduct levels as demonstrated by 32P-postlabeling technique (P < 0.05). Western blotting analysis indicated that HC pretreatment induced the expression of cyclooxygenase-2 (COX-2) and dihydrodiol dehydrogenase (DDH). COX-2 is know to participate in the B[a]P-DNA adduct formation, while DDH has been shown to divert B[a]P-diol to B[a]P-7,8-quinone and the generation of reactive oxygen species (ROS). Using flow cytometry, this study demonstrated the increased production of 8-oxoguanine (P < 0.001). Overall, the results suggest that HC-induced DDH is more important than site-by-site up-regulation of COX-2 in B[a]P-induced cytotoxicity and HPRT gene mutation. Furthermore, DDH-mediated oxidative DNA damage and not B[a]P-DNA adduct formation may be involved in the HC and B[a]P-induced toxic effects.
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PMID:Hydroxychavicol modulates benzo[a]pyrene-induced genotoxicity through induction of dihydrodiol dehydrogenase. 1533 Nov 32