Profiling of biomarkers for the exposure of polycyclic aromatic hydrocarbons: lamin-A/C isoform 3, poly[ADP-ribose] polymerase 1, and mitochondria copy number are identified as universal biomarkers.

This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-) induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number) was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs.

New strategy for detection of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes based on cardiac multi-detector computed tomography and treadmill test.

BACKGROUND: The current screening strategy for subclinical coronary atherosclerosis in asymptomatic diabetic patients is not sufficient in real clinical practice. A new strategy was investigated that uses cardiac multi-detector computed tomography (MDCT) and a treadmill test (TMT). METHODS AND RESULTS: A total of 445 self-referred asymptomatic diabetic patients underwent cardiac MDCT. The treatment plan was determined according to the new strategy that uses MDCT and TMT. All patients underwent clinical follow-up and cardiac events were investigated. The incidence of subclinical atherosclerosis was 49.4%. The group without plaque underwent clinical follow-up without treatment and did not experience any cardiac events in 675.1 person-years of follow-up. Among patients with subclinical atherosclerosis without significant stenosis (n=136) who received medical treatment only, 11 patients experienced cardiac events over 326.4 person-years. The patients with significant stenosis (n=84) underwent TMT. Patients with positive TMT (n=14) underwent coronary angiograms and revascularization therapy was performed in all of them over 39.2 person-years. Patients with negative TMT (n=70) underwent medical treatment, and 27 of them experienced cardiac events. The incidence of cardiac death was 0% during 3 years of follow-up. CONCLUSIONS: The new strategy for detecting subclinical atherosclerosis on MDCT combined with TMT may be a useful method for minimizing the mortality rate from cardiovascular disease in asymptomatic diabetic patients.

Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.

Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk.

Endoneurial microangiopathy of sural nerve in experimental vacor-induced diabetes.

The pathogenic mechanism of diabetic peripheral neuropathy is multifactorial. This study investigated microangiopathic changes of endoneurial vessels of sural nerve in Vacor-induced diabetic rats. Experimental rats were divided into 3 groups: acute (80 mg/kg, once), chronic diabetic (8 mg/kg, 14 times), and control. Ultrastructural morphometric parameters of endoneurial microvessels, blood glucose, and body weight changes were statistically analyzed, and correlations among the variables were evaluated. The body weight and blood glucose levels were significantly different between the control and diabetic rats. The blood glucose was more significantly elevated in the acute diabetic rats than the chronic diabetic rats. Inner and outer vascular circumference, vascular area, luminal area, basement membrane area, and basement membrane thickness were significantly increased in the acute diabetic rats compared to the control group, but not between the chronic diabetic rats and the control group. The thickness of basement membrane was positively correlated with hyperglycemia and body weight loss (P < .01). These results suggest that the microangiopathy of the peripheral nerve could be developed in acute Vacor-induced diabetes. The decreased perfusion through microangiopathic endoneurial vessels appears to have a pathogenic role causing diabetic peripheral neuropathy.