Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer

Cheng, Tsun‐Jen; Christiani, David C.; Liber, Howard L.; Wain, John C.; Xu, Xiping; Wiencke, John K.; Kelsey, Karl T.

doi:10.1016/0027-5107(95)00161-8

Cited by 18 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In at-risk populations including smokers, patients with DNA repair deficiency syndromes, and atom bomb survivors there are significant mutations in the HPRT locus that directly corresponds with higher cancer incidence (Branda, O"Neill, Jacobson-Kram, & Albertini, 1992;Cheng et al, 1995;Duthie, Ross, & Collins, 1995;Hakoda, Akiyama, Kyoizumi, & Awa, 1988;Hou et al, 1999;Robinson et al, 1994;Sawada et al, 1998;Tates, Dam, Natarajan, Zwinderman, & Osanto, 1994). While its role as a standard mutational biomarker for cancer development has been well established, the relevance of HPRT to the proliferative capacity and tumorigenesis of cancer has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue

Townsend¹,

Felsted²,

Ence³

et al. 2017

CCO

View full text Add to dashboard Cite

Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) is a housekeeping enzyme involved in the purine synthesis of guanine and inosine in the salvage pathway. While other salvage pathway enzymes, such as TK1, have been established as biomarkers for both cancer cell proliferation and cancer development, little research been done to evaluate whether HPRT has the same potential as a cancer biomarker. We designed this study to determine if HPRT has value as an identifier of malignancy within the most common types of cancer. We utilized histological samples from lung, colon, prostate, and breast cancer with additional normal tissue to evaluate whether there was any elevation of HPRT within malignant samples. In addition, we also assessed general HPRT expression within patient"s samples from The Cancer Genome Atlas (TCGA) to confirm clinical relevance. We found that within a subset of patients, there was significant elevation of HPRT when compared to normal tissue controls. This elevation was seen in 33-55% of the malignant samples and appears to have no dependence on cancer stage. There were slight differences in staining patterns among all the organ types, but overall each organ displayed the same pattern of "HPRT high" and "HPRT low" populations within malignant samples. We found that in our TCGA samples, there was a similar elevation of HPRT that was significant when compared to normal controls. Overall, as an upregulated enzyme that does not directly correlate with stage, HPRT could become a valuable marker in the early diagnosis of a variety of solid tumors.

show abstract

Section: Introductionmentioning

confidence: 99%

Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue

Townsend¹,

Felsted²,

Ence³

et al. 2017

CCO

View full text Add to dashboard Cite

show abstract

“…In addition, in these studies the overall genotoxic effect of treatment on HPRT Mf in children treated for ALL could not be determined since the Mfs at the time of diagnosis were unknown. Mutant frequency analysis in adult malignancies including testicular , lung [Cheng et al, 1995], and breast cancer [Bigbee et al, 1990] revealed that HPRT Mf and glycophorin A (GPA) variant frequency (V f ) were not significantly elevated compared to age-matched controls prior to treatment. This study demonstrates that there is no elevation in background somatic mutant frequency in children at the time of diagnosis with cancer.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of HPRT mutant frequency in children with cancer

Rice

Vacek

Homans

et al. 2003

Environ and Mol Mutagen

View full text Add to dashboard Cite

The link between exposure to environmental mutagens and the development of cancer is well established. Yet there is a paucity of data on the relationship between gene-environment interactions and the mechanisms associated with the somatic mutational events involved with malignant transformation, especially in children. To gain insight into somatic mutational mechanisms in children who develop cancer, we determined the background mutant frequency (Mf) in the hypoxanthine phosphoribosyl transferase (HPRT) reporter gene of peripheral blood lymphocytes from pediatric cancer patients at the time of diagnosis and prior to therapeutic intervention. We studied 23 children with hematologic malignancies and 31 children with solid tumors prior to initial therapeutic intervention. Children with solid tumors, specifically sarcomas, and Hodgkin's disease were significantly older and had elevated HPRT Mfs (6.1 x 10(-6) and 3.7 x 10(-6), respectively) at the time of diagnosis, compared to normal controls (2.3 x 10(-6)) and other pediatric tumor groups including children with acute lymphocytic leukemia and non-Hodgkin's lymphoma (ALL/NHL, 1.7 x 10(-6)), central nervous system tumors (CNS, 3.6 x 10(-6)), and neuroblastoma (1.9 x 10(-6)). Of importance is that the significant differences observed in HPRT Mfs between these groups no longer existed after correcting for the effects of age. These data demonstrate that in children who develop cancer there appears to be no significant increase in background HPRT Mf that would indicate significant exposure to genotoxic chemicals or an underlying DNA repair defect resulting in genomic instability. In addition, these data demonstrate the importance of correcting for the effect of age when comparing the frequency of somatic mutations in children and should provide baseline data for future longitudinal biomonitoring studies on the genetic effects of chemotherapy in children treated for cancer.

show abstract

“…A similar effect was not found in former or current smokers. In the same group the mutant frequency at the HPRTlocus (71) and micronuclei in human lymphocytes (72) were studied. Mutant frequency at HPRTand micronuclei frequency were not associated with GSTM] polymorphism.…”

Section: Environmental Exposure To Mutagens and Carcinogensmentioning

confidence: 99%

Effect of glutathione S-transferase M1 polymorphisms on biomarkers of exposure and effects

Šrám¹

1998

Environ Health Perspect

View full text Add to dashboard Cite

Genotypes responsible for interindividual differences in ability to activate or detoxify genotoxic agents are recognized as biomarkers of susceptibility. Among the most studied genotypes are human glutathione transferases. The relationship of genetic susceptibility to biomarkers of exposure and effects was studied especially in relation to the genetic polymorphism of glutathione S-transferase M1 (GSTM1). For this review papers reporting the effect of GSTM1 genotype on DNA adducts, protein adducts, urine mutagenicity, Comet assay parameters, chromosomal aberrations, sister chromatid exchanges (SCE), micronuclei, and hypoxanthine-guanine phosphoribosyl transferase mutations were assessed. Subjects in groups occupationally exposed to polycyclic aromatic hydrocarbons, benzidine, pesticides, and 1,3-butadiene were included. As environmentally exposed populations, autopsy donors, coal tar-treated patients, smokers, nonsmokers, mothers, postal workers, and firefighters were followed. From all biomarkers the effect of GSTM1 and N-acetyl transferase 2 was seen in coke oven workers on mutagenicity of urine and of glutathione S-transferase T1 on the chromosomal aberrations in subjects from 1,3-butadiene monomer production units. Effects of genotypes on DNA adducts were found from lung tissue of autopsy donors and from placentas of mothers living in an air-polluted region. The GSTM1 genotype affected mutagenicity of urine in smokers and subjects from polluted regions, protein adducts in smokers, SCE in smokers and nonsmokers, and Comet assay parameters in postal workers. A review of all studies on GSTM1 polymorphisms suggests that research probably has not reached the stage where results can be interpreted to formulate preventive measures. The relationship between genotypes and biomarkers of exposure and effects may provide an important guide to the risk assessment of human exposure to mutagens and carcinogens.

show abstract

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer

Cited by 18 publications

References 29 publications

Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue

Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue

Comparative analysis of HPRT mutant frequency in children with cancer

Effect of glutathione S-transferase M1 polymorphisms on biomarkers of exposure and effects

Contact Info

Product

Resources

About