Expression variation of OGG1 and HPRT gene and DNA damage in arsenic exposed industrial workers

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage in blood cells by comet assay along with age and gender matched 300 control individuals. Blood arsenic content was higher (P\u3c0.001) in an industrial group compared to the control. OGG1 and HPRT expression were (P\u3c0.05) downregulated in exposed workers compared to controls. Spearman correlation analysis showed a significant positive correlation between HPRT vs OGG1 (P\u3c 0.0001) in exposed workers compared to controls. Altered expression of both genes was observed between workers with \u3c25years and \u3e25years of age as well as between workers with \u3c10years and \u3e10year exposure. Reduced expression (P\u3c0.05) of both genes and a high extent of DNA damage was evident in exposed smokers compared to respective non-smokers. DNA fragmentation was higher (P\u3c0.05) in the furniture, welding and brick kiln group compared to control, and other industries. The present study suggests that altered expression of OGG1 and HPRT gene induce oxidative stress, showed a negative impact on the recycling of purines leading to DNA damage which increase the vulnerability of workers to carcinogenicity

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Different comet parameters associated with comet head and tail measured by comet assay in smokers (S) and non-smokers (NS) of exposed workers from different industries.

*P<0.05, **P<0.01, ***P<0.001.</p

Arsenic content in blood samples of controls and workers of different industries.

Arsenic content in blood samples of controls and workers of different industries.</p

Primer sequence of <i>HPRT</i>, <i>OGG1</i> and <i>β-actin</i> gene.

Primer sequence of HPRT, OGG1 and β-actin gene.</p

Fluorescence photomicrograph of blood lymphocytes from control and furniture group stained with Acridine Orange after processed through Single Cell Gel Electrophoresis (Comet assay).

Fluorescence photomicrograph of blood lymphocytes from control and furniture group stained with Acridine Orange after processed through Single Cell Gel Electrophoresis (Comet assay).</p

Comparison of different comet parameters between control and different industries.

Comparison of different comet parameters between control and different industries.</p

Fig 6 -

Deposition of metal content (arsenic, lead, cadmium) in blood samples of occupationally exposed workers of different industries (A). Calculated regression line showing metal deposition in control and exposed workers ((b = 2.718 ± 0.01367; F (1,2) = 39521; P = 0.0032) (B). Association of arsenic content with different parameters of comet assay (C). ***P<0.001.</p

Demographic data of control and exposed group of furniture, paint, welding, pesticide and brick kiln industry.

Demographic data of control and exposed group of furniture, paint, welding, pesticide and brick kiln industry.</p