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)

We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective study of hprt mutant and mutation frequencies in treated cancer patients. 130 70

We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.
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PMID:Effect of high-dose methotrexate on plasma hypoxanthine and uridine levels in patients with acute leukemia or non-Hodgkin lymphoma in childhood. 143 5

The frequency of sister chromatid exchanges (SCEs) was determined in Hodgkin's disease (HD) patients prior to therapy, following radiotherapy, and following combined radiotherapy and chemotherapy. The frequency of hprt- mutants in these patients has been reported previously. The frequency of SCEs and hprt- mutants in the same individuals were compared. In non-HD controls the mean SCE frequency and the mean of high SCE frequency cells (HFCs) were significantly increased by smoking, while mutant frequency (MF) showed no effect. Untreated HD patients had mean SCEs, mean HFCs and mean MFs that were higher than non-MD controls. In treated patients, mean SCE and HFC frequencies were lower than untreated patients and non-HD controls, while their MFs were significantly elevated. Overall, SCE frequency was not correlated with MF in control or HD patient groups, suggesting that these biomarkers may reflect, in this case, fundamental biological differences between these processes.
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PMID:Sister chromatid exchange frequency in Hodgkin's disease patients with elevated in vivo hprt mutant frequencies. 193 1

A subset of Hodgkin's disease (HD) and breast cancer patients have been reported to have elevated hprt mutant frequencies in peripheral blood lymphocytes after cessation of therapy. A subset of these patients are also known to develop second therapy-related malignancies. Therefore, it is clearly important to determine if these elevations in mutant frequency represent true, persistently elevated mutation frequencies. As a follow-up to our study of patients previously treated for HD, we recruited for a prospective study six previously treated HD patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7 months. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single strand conformation polymorphisms at the T-cell receptor-gamma locus of individual mutant clones. This analysis showed that 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients were siblings. The sibling mutants generally did not persist over time. However, one patient had one mutant clone that persisted, but slowly decreased in prevalence over a 7 month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutagenesis after cancer therapy. 814 13

Therapy for Hodgkin's disease has been associated with a significant increase in risk for second cancers. To begin an investigation of the association of therapy-induced genetic damage with this risk, somatic mutations at the hypoxanthine phosphoribosyltransferase locus were measured in lymphocytes from patients previously treated for Hodgkin's disease. The results demonstrate that a subset of patients have persistently elevated mutation frequencies, perhaps suggesting that these individuals are among those at significant risk of second cancer development.
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PMID:Mutagenesis after therapy for Hodgkin's disease. 846 70

In vivo measurement of human somatic mutations may be a valuable biodosimeter of exposure to carcinogens and of cancer risk. We have surveyed translocations at the bcl2 locus in B lymphocytes, and mutations at hprt in T lymphocytes, in 120 individuals with varying exposure to radon and cigarette smoke. bcl2 t(14:18) translocation is the commonest chromosomal alteration observed in non-Hodgkins lymphoma (NHL). We observed a significantly larger range of bcl2 translocation frequency (range: 0-372 x 10(-6), median: 1.9 x 10(-6)) than of hprt mutation frequency (range: 0-76.4 x 10(-6), median: 11.1 x 10(-6)), which is likely the result of clonal proliferation of deathless B cell mutants. We observed that the frequencies of these two distinct lymphocytic mutations are significantly correlated. Although some of the correlated variation is explained by age, a significant correlation of bcl2 mutagenesis persists after age adjustment. Correlated mutagenesis at distinct loci in distinct cell types could be explained by the existence of a mutator phenotype or by variation in exposure to environmental mutagens. NHL is commoner in men than in women, and our data indicate a trend toward higher bcl2 mutagenesis in males than females. There is mounting epidemiological evidence for a worldwide increase in NHL, which may have an environmental basis; molecular epidemiological analysis of bcl2 mutagenesis in exposed populations might be especially relevant to the identification of putative environmental causes. Given the relative ease of the bcl2 assay versus the hprt assay, and the consistency with which data are reproduced from laboratory to laboratory, it is likely that the bcl2 assay will be soon added to the array of assays used in human mutational surveillance.
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PMID:Correlated mutagenesis of bcl2 and hprt loci in blood lymphocytes. 902 Mar 5

Validity of measurement of somatic cell mutation frequency (Mf) at the hprt locus for evaluating cancer risk of the given individual was determined in pediatric patients. Peripheral lymphocytes (PL) from patients with various diseases, including acute lymphoblastic leukemia (ALL) and Hodgkin's disease (HD), DNA repair deficient syndromes or short stature receiving growth hormone (GH), were isolated through Ficoll-Hypaque sedimentation with informed consent. Mf at the hprt locus of PL was determined by limiting dilution assay using 6-thioguanine (6-TG). Results were as follows. (1) ALL patients after chemotherapy had higher Mf than that of age-matched controls. (2) Patients with HD tended to have higher Mf after chemotherapy. (3) Among DNA-repair deficient syndromes, diseases which are susceptible to cancer (Xeroderma pigmentosum, Ataxia telangiectasia) have high Mf, but those without any cancer disposition (Cockayne syndrome, Rothmund-Thomson syndrome) have normal Mf. (4) GH-receiving patients have normal Mf, regardless of total doses of GH. Measurement of Mf at HPRT locus may be useful for evaluating cancer risk of pediatric patients.
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PMID:Measurement of mutation frequency at the HPRT locus in peripheral lymphocytes. Is this a good method to evaluate a cancer risk in pediatric patients? 959 52