A Combination of Single Nucleotide Polymorphisms is Associated with the Interindividual Variability of Cholesterol Bioavailability in Healthy Adult Males
MOLECULAR NUTRITION & FOOD RESEARCH
Authors: Desmarchelier, Charles; Wolff, Estelle; Defoort, Catherine; Nowicki, Marion; Morange, Pierre-Emmanuel; Alessi, Marie-Christine; Valero, Rene; Nicolay, Alain; Lairon, Denis; Borel, Patrick
Abstract
Scope Cholesterol bioavailability displays a high interindividual variability, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explained a minor fraction of the variability of this complex phenotype. The aim is to identify a combination of SNPs associated with a significant part of the variability in cholesterol bioavailability. Methods and results Thirty-nine healthy adult males are given a standard test snack containing 80 mg heptadeuterated (D7) cholesterol. The plasma D7-cholesterol concentration is measured at equilibrium 40 h after test snack intake. The D7-cholesterol response (D7-cholesterol/total cholesterol concentration) exhibits a relatively high interindividual variability (CV = 32%). The association of exonic SNPs in candidate genes (188 genes involved in or related to cholesterol metabolism) with the plasma D7-cholesterol response is assessed by univariate statistics followed by partial least squares regression. A significant model (p-value after cross-validation ANOVA = 1.64 x 10(-7)) that includes 8 SNPs (SOAT2-rs9658625,DNAH11-rs11768670,LIPC-rs690,MVK-rs2287218,GPAM-rs10787428,APOE-rs7412,CBS-rs234706, andWRN-rs1801196) explains 59.7% of the variance in cholesterol bioavailability (adjustedR(2)). Conclusion Here a combination of SNPs is significantly associated with the variability in dietary cholesterol bioavailability in healthy adult males.
The effects of Efaproxyn (TM) (Efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice
RADIATION RESEARCH
Authors: Hou, Huagang; Khan, Nadeem; Grinberg, Oleg Y.; Yu, Hongsheng; Grinberg, Stalina A.; Lu, Shiyi; Demidenko, Eugene; Steffen, Robert P.; Swartz, Harold M.
Abstract
Efaproxiral, an allosteric modifier of hemoglobin, reduces hemoglobin-oxygen binding affinity, facilitating oxygen release from hemoglobin, which is likely to increase tissue pO(2). The purpose of this study was to determine the effect of efaproxiral on tumor oxygenation and growth inhibition of RIF-1 tumors that received X radiation (4 Gy) plus oxygen breathing compared to radiation plus oxygen plus efaproxiral daily for 5 days. Two lithium phthalocyanine (LiPc) deposits were implanted in RIF-1 tumors in C3H mice for tumor pO(2) measurements using EPR oximetry. Efaproxiral significantly increased tumor oxygenation by 8.4 to 43.4 mmHg within 5 days, with maximum increases at 22-31 min after treatment. Oxygen breathing alone did not affect tumor pO(2). Radiation plus oxygen plus efaproxiral produced tumor growth inhibition throughout the treatment duration, and inhibition was significantly different from radiation plus oxygen from day 3 to day 5. The results of this study provide unambiguous quantitative information on the effectiveness of efaproxiral to consistently and reproducibly increase tumor oxygenation over the course of 5 days of treatment, modeling the clinical use of efaproxiral. Also, based on the tumor growth inhibition, the study shows the efaproxiral-enhanced tumor oxygenation was radiobiologically significant. This is the first study to demonstrate the ability of efaproxiral to increase tumor oxygenation and to increase the tumor growth inhibition of radiotherapy over 5 days of treatment. (c) 2007 by Radiation Research Society.