Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

V79 Chinese hamster cells were cultured in the presence of 3-methylcholanthrene-diolepoxide (10r,9t-dihydroxy-7,8t-epoxy-tetrahydro-3-methylcholanthrene, MCDE) and mutants were selected in medium containing 6-thioguanine (TG). Of 22 TG-resistant mutants examined, 18 were devoid of HPRT (hypoxanthine-guanine phosphoribosyltransferase, EC 2.4.2.8) activity. Two mutants had suffered a total and one a partial gene deletion. The 1.6-kb HPRT mRNA was not detected in these three mutants nor in two others. The remaining mutants did not, however, have a readily demonstrable lesion.
Carcinogenesis 1985 Oct
PMID:On the mechanism of induction of resistance to 6-thioguanine in Chinese hamster V79 cells by 3-methylcholanthrene-diolepoxide. 299 1

The formation of DNA adducts by the ultimate carcinogen 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (BPDE-I) has been implicated in the process of carcinogenesis. In a line of Chinese hamster ovary (CHO) cells designated AT3-2 and in two derivative mutant lines, UVL-1 and UVL-10, originally selected for hypersensitivity to UV-irradiation, we have measured the formation of BPDE-I: DNA adducts and the production of biological damage. The quantity and quality of BPDE-I: DNA adducts formed initially in the 3 cell lines are identical over a wide range of BPDE-I doses. However, the UVL lines are unable to remove adducts from their DNA, while the AT3-2 cells remove about 50% of the BPDE-I: DNA adducts in a 24-h incubation. Correlated with this, the UVL lines are more sensitive to the lethal effects of BPDE-I than are the AT3-2 cells. Mutant frequencies were measured at the aprt, hprt and oua loci and were found to increase linearly with BPDE-I: DNA adduct formation at doses which gave greater than 50% survival. At the hprt and oua loci, the efficiency of mutation induction was similar for AT3-2 and UVL-10 cells. UVL-1 cells showed slightly higher (within a factor of 2-3) mutant frequencies in response to BPDE-I compared to AT3-2 at these two loci. However, at the aprt locus the repair-deficient cells were much more highly mutable (9-15-fold) than the repair-proficient AT3-2 cells. Based on the measured average level of adduct formation, it is calculated that 15% of the BPDE-I: DNA adducts in the aprt gene are converted into mutations. However, the possibility exists that the aprt locus is subject to higher levels of modification by BPDE-I than is the bulk DNA, which would lead to an artifactually high apparent conversion frequency.
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PMID:Differential efficiency of mutagenesis at three genetic loci in CHO cells by a benzo[a]pyrene diol epoxide. 312 54

DNA prelabelled in the purine or pyrimidine bases was reacted with anti-7,8-epoxy-trans-9,10-dihydroxy-7,8,9,10-tetra-hydro-3-methylchol ant hrene (anti-3MCDE). Enzymic degradation and column chromatography allowed the isolation of a number of hydrocarbon--nucleoside derivatives. The major product was shown to result from reaction with the 2-amino-group of guanine, but minor products containing guanine, adenine and cytosine were also obtained. One of the minor products, probably resulting from reaction at N7-guanine, led to rapid depurination. Anti-3MCDE was an efficient mutagen at the hprt-locus of V79 cells even at low doses which caused no cytotoxicity. In all the above properties anti-3MCDE closely resembled the anti-diol-epoxide of benzo[a]-pyrene. A similar study of DNA derived from mouse embryo cells which had been exposed to tritium labelled 3-methylcholanthrene (3MC) yielded a series of nucleoside adducts, only a minority of which were derived by reaction of anti-3MCDE with DNA. Two major in vivo products were shown to derive from 3MC alcohols, particularly 3-hydroxymethyl-cholanthrene, and probably involved both syn and anti-diol-epoxide metabolites.
Carcinogenesis 1986 Aug
PMID:The reaction of a 3-methylcholanthrene diol epoxide with DNA in relation to the binding of 3-methylcholanthrene to the DNA of mammalian cells. 373 88

The two pairs of diastereomeric anti- and syn-diolepoxide derivatives of 5-methylchrysene in both bay regions were tested for cytotoxicity and for mutagenicity at the hprt locus of chinese hamster V79 cells as determined by the ability of the cells to form colonies in medium containing 6-thioguanine. The concentration of compound in the cell media required to achieve 37% survival ranged from 0.3 to 4.5 micrograms/ml. Although the mutagenic effectiveness, i.e. the induced mutation frequency per unit concentration of compounds, varied over a 30-fold range, the mutagenic efficiency, i.e. the induced mutation frequency at an equivalent level of cell survival, showed only a 3-fold variation. The anti-1,2-diol-3,4-epoxide isomer (anti-5MCDE-I) was found to be the most mutagenic of the 5-methylchrysene diolepoxide isomers. This finding is consistent with previous observations on the tumorigenicity of these diolepoxides.
Carcinogenesis 1986 Mar
PMID:Mutation in mammalian cells by isomers of 5-methylchrysene diolepoxide. 375 6

We have previously described the induction by r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) of 8-azaguanine resistant (AGr) Chinese hamster V79 cell mutants, 40% of which were found to contain material which cross-reacted (CRM) with antiserum to hypoxanthine-guanine phosphoribosyltransferase (HPRT) and whose AGr phenotype we ascribed to missense mutation (Brookes et al., 1982). We now report that we have been unable to demonstrate by Southern blotting any change in the HPRT gene in 11 CRM-negative mutants. We have, moreover, found HPRT mRNA of normal size and amount in most of these mutants. Examination of the revertants of one mutant indicates the probable occurrence of changes within an amino acid codon in the genesis of mutant and revertant. Our results suggest that BPDE functions primarily as a point mutagen.
Carcinogenesis 1984 Jul
PMID:On the nature of the mutations induced by the diolepoxide of benzo[a]pyrene in mammalian cells. 632 42

Combined cultures of human hepatocytes and human fibroblasts constitute a system composed entirely of normal human cells that can be used to investigate the mutagenicity of chemicals requiring metabolic activation. Addition of diethylnitrosamine (DEN) to this system resulted in mutations at the hypoxanthine-guanine phosphoribosyltransferase locus of the human fibroblasts. In separate experiments with cultures of hepatocytes alone, DEN induced unscheduled DNA synthesis (UDS) in the human hepatocytes. A comparative analysis of UDS and hepatocyte-mediated mutagensis indicates a great degree of similarity between the human and previously studied rat hepatocytes in their response to DEN in vitro.
Carcinogenesis 1983
PMID:Human hepatocyte-mediated mutagenesis and DNA repair activity. 640 71

A series of 8-azaguanine resistant mutants was induced by treatment of V79 Chinese hamster cells with either r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (antiBPDE) or methylnitrosourea (MNU). Hypoxanthine phosphoribosyltransferase (HPRT) activity in the mutants was determined for both hypoxanthine and azaguanine as substrates. With antiserum to purified brain HPRT, cross-reacting material was also determined and analysed by two dimensional polyacrylamide gel electrophoresis. By these criteria mutants induced by anti-BPDE or MNU did not differ appreciably and the data obtained was consistent with the induction of point mutations by both carcinogens. The relevance of these results to the correlation of carcinogenicity with mutagenicity in V79 cells, but not in bacteria, is discussed.
Carcinogenesis 1982
PMID:Biochemical and immunological characterisation of mutants induced in V79 Chinese hamster cells by a benzo[a]pyrene diolepoxide. 681 Nov 44

A murine keratinocyte cell-mediated mutagenesis assay was characterized and examined as an in vitro model system for studying the biotransformation of promutagens/procarcinogens by mouse skin. The assay used living cultured newborn SENCAR keratinocytes for the metabolic activation of promutagens and Chinese hamster lung V-79 fibroblasts for detection of resulting mutagens. Mutations at, or affecting, the hypoxanthine-guanine phosphoribosyltransferase locus were scored by resistance to 6-thioguanine. The relative mutagenicities of several polycyclic aromatic hydrocarbons (PAHs) in the cell-mediated assay correlated with the in vivo skin tumorigenicity of the PAHs determined in a two-stage carcinogenesis protocol. Metabolic activation of the promutagenic PAHs to ultimate mutagens was dependent upon the presence of the cultured keratinocyte feeder layer. 7,8-Benzoflavone, a potent inhibitor of 7,12-dimethylbenz[a]anthracene (DMBA)-dependent initiation in mouse skin, inhibited DMBA-dependent mutagenesis in the cell-mediated assay in a concentration responsive manner. The non-PAH promutagens, dimethylnitrosamine (DMN) and sterigmatocystin (STC) were both activated by cultured keratinocytes to cytotoxic derivatives. DMN was neither mutagenic in the cell-mediated assay nor tumorigenic in mouse skin when tested in a two-stage carcinogenesis protocol. STC was weakly mutagenic and tumorigenic in mouse skin.
Carcinogenesis 1983
PMID:Keratinocyte cell-mediated mutagenesis assay: correlation with in vivo tumor studies. 683 37

Cocultures were established of a cell line deficient in hypoxanthine-guanine phosphoribosyltransferase (PG-19; HPRT-) and a mouse epidermal cell line (HEL-37; HPRT+). The cocultures were incubated in a medium containing hypoxanthine, aminopterin and thymidine (HAT). HPRT- cells die in HAT medium unless rescued by metabolic cooperation with HPRT+ cells. The extent of cell death was measured by the release of radioactivity from PG-19 cells previously labelled with [3H]thymidine, and expressed as the lytic index. The lytic index was significantly increased (decreased metabolic cooperation) by tumor-promoting phorbol esters but not by non-promoting esters. The enhanced lytic index was obtained when promoters were incubated with cocultures for 10 h in a total incubation time of 48 h.
Carcinogenesis 1981
PMID:Tumor promoter inhibition of intercellular communication between cultured mammalian cells. 727 7

Treatment of cultures of spontaneously immortalized human epidermal cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitized them to carcinogen toxicity. While the tryptophan pyrolysis product 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and the mycotoxin sterigmatocystin were highly toxic to the cultures at moderate concentration (1 microgram/ml), the potency of each agent was increased > or = 10-fold in the presence of TCDD. A toxicity increase was also evident in the several-fold stimulation by TCDD of protein and DNA adducts formed by Trp-P-1. In contrast, the cells were insensitive to toxicity from 3-amino-1-methyl-5H-pyrido[4,3-b]indole. DNA damage mediated by Trp-P-1 was capable of producing inheritable effects, as judged by the induction of hprt mutants in a TCDD-stimulated fashion. Northern blotting showed that TCDD strongly stimulated expression of P4501A1 and 1B1 in the cells, enzymes important for xenobiotic metabolism. These findings demonstrate the potential usefulness of SIK cultures as a model for studying keratinocyte responses to carcinogens activated by TCDD-induced cytochromes P450.
Carcinogenesis 1995 Sep
PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin sensitization of cultured human epidermal cells to carcinogenic heterocyclic amine toxicity. 755 73


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