Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population.

Aim: To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs). Materials & methods: Eleven variants in seven candidate genes were genotyped in 127 pediatric acute lymphoblastic leukemia patients under 6-mercaptopurine (6-MP) treatment to infer the association of selected genotypes with TRAEs. Results: Among the genotypes inspected, NUDT15 (c.415C>T) and SLC19A1 (c.80G>A) showed a significant association with the TRAEs (odds ratio = 4.01, p = 0.002 and odds ratio = 7.78, p = 0.002). Conclusion:SLC19A1 and NUDT15 play an important role in the metabolism of 6-MP and it is necessary to spot other variants in associated pathways and investigate the factors that can impact 6-MP metabolism.

Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study.

BACKGROUND: Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes. MATERIALS AND METHODS: Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 µT for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired't' test. RESULTS: In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 µT and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P < 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 µT field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 µT PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters. CONCLUSIONS: Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).

Radiation signature on exposed cells: Relevance in dose estimation.

The radiation is considered as a double edged sword, as its beneficial and detrimental effects have been demonstrated. The potential benefits are being exploited to its maximum by adopting safe handling of radionuclide stipulated by the regulatory agencies. While the occupational workers are monitored by personnel monitoring devices, for general publics, it is not a regular practice. However, it can be achieved by using biomarkers with a potential for the radiation triage and medical management. An ideal biomarker to adopt in those situations should be rapid, specific, sensitive, reproducible, and able to categorize the nature of exposure and could provide a reliable dose estimation irrespective of the time of the exposures. Since cytogenetic markers shown to have many advantages relatively than other markers, the origins of various chromosomal abnormalities induced by ionizing radiations along with dose-response curves generated in the laboratory are presented. Current status of the gold standard dicentric chromosome assay, micronucleus assay, translocation measurement by fluorescence in-situ hybridization and an emerging protein marker the γ-H2AX assay are discussed with our laboratory data. With the wide choice of methods, an appropriate assay can be employed based on the net.

Genetic variation of GSTM1, GSTT1 and GSTP1 genes in a South Indian population.

The glutathione S transferase (GST) family of enzymes play a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and the polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. Moreover, distinct ethnic differences have been observed in the type and frequency of GST gene polymorphisms. Hence, the present study was aimed to determine the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 255 healthy random volunteers from South India. The GSTM1 and GSTT1 genotypes were determined by PCR and GSTP1 by PCR-RFLP using peripheral blood DNA. The GSTM1 and GSTT1 null genotype frequencies were found to be 22.4% and 17.6% respectively. The GSTP1 allelic frequency was 0.78 for the Ile allele and 0.22 for the Val allele and the genotype frequency was 58.4% for Ile/Ile, 38.4% for Ile/Val, and 3.1% for Val/Val. Comparison of the frequencies of GST polymorphisms observed in the present study with other Indian and world populations revealed a distinctive nature of the South Indian population with respect to polymorphims at the GST gene loci. A better understanding of carcinogen metabolizing gene distribution should contribute to risk assessment of humans exposed to environmental carcinogens.