The influence of smoking and diet on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in circulating T lymphocytes from a normal human population

Duthie, Susan J.; Ross, Marion A.; Collins, Andrew

doi:10.1016/0027-5107(95)00051-j

Cited by 28 publications

(10 citation statements)

References 42 publications

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“…At the beginning and at the end of the study, 10 ml blood was collected in heparinized tubes (BN Vacutainer Systems, Plymouth, UK). Lymphocytes were isolated using Histopaque-1077 (density 1.077 g/L) according to Duthie et al [38]. After the first centrifugation (10 min, 48C, 6506g), plasma was collected and stored at -808C.…”

Section: Intervention Studiesmentioning

confidence: 99%

Consumption of Brussels sprouts protects peripheral human lymphocytes against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and oxidative DNA‐damage: results of a controlled human intervention trial

Hoelzl

Glatt

Meinl

et al. 2008

Molecular Nutrition Food Res

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To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.

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Section: Intervention Studiesmentioning

confidence: 99%

Consumption of Brussels sprouts protects peripheral human lymphocytes against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and oxidative DNA‐damage: results of a controlled human intervention trial

Hoelzl

Glatt

Meinl

et al. 2008

Molecular Nutrition Food Res

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“…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

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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.

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“…Peripheral lymphocytes were isolated from 10 ml venous blood of a healthy male donor (non-smoker, 39 years) using a separation medium with a density of 1.077 g/l (Histopaque-1077, Sigma, St. Louis, USA) according to the protocol of Duthie et al [22]. The cells were suspended in PBS buffer solution.…”

Section: Scge Test With Primary Human Lymphocytesmentioning

confidence: 99%

Investigation of the genotoxic effects of 2-amino-9H-pyrido[2,3-b]indole in different organs of rodents and in human derived cells

Majer

Kassie

Sasaki

et al. 2004

Journal of Chromatography B

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The influence of smoking and diet on the hypoxanthine phosphoribosyltransferase (hprt) mutant frequency in circulating T lymphocytes from a normal human population

Cited by 28 publications

References 42 publications

Consumption of Brussels sprouts protects peripheral human lymphocytes against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and oxidative DNA‐damage: results of a controlled human intervention trial

Consumption of Brussels sprouts protects peripheral human lymphocytes against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and oxidative DNA‐damage: results of a controlled human intervention trial

Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue

Investigation of the genotoxic effects of 2-amino-9H-pyrido[2,3-b]indole in different organs of rodents and in human derived cells

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