North Eastern Hill University

About: North Eastern Hill University is a education organization based out in Shillong, Meghalaya, India. It is known for research contribution in the topics: Population & Catalysis. The organization has 2318 authors who have published 4476 publications receiving 48894 citations.

Modulation of mitomycin C-induced sister chromatid exchanges and cell cycle delay by buthionine sulfoximine and reduced glutathione in mouse bone marrow cells in vivo.

Abstract: Mitomycin C (MMC) is a bifunctional alkylating agent and a chemotherapeutic drug, covalently binds to the DNA of cells and produces monoadducts and DNA-DNA, DNA-protein crosslinks, induces damages at chromosomal level and slows down the rate of cell proliferation. Reduced glutathione (GSH), a major non-protein thiol substance plays an important role in detoxification of cells against the toxic effect of exogenous compounds. In order to understand the role of factor which affects MMC sensitivity, we have made an attempt to establish a relationship between MMC-induced DNA damages and the endogenous GSH-status of the cells. MMC was treated to normal and buthionine sulfoximine (BSO; GSH-depleting agent)-treated mice. Exogenous GSH was also added to MMC-treated normal mice. Cells were fixed at 24 h and sister chromatid exchanges (SCEs) and average generation time (AGT) were scored. MMC-induced SCEs and cell cycle delay significantly with respect to control and the frequency of SCEs was increased considerably while MMC treatment combined with either GSH or BSO. The induction of cell cycle delay by MMC was reduced significantly when GSH or BSO was present along with MMC. These observations indicate that the factor responsible for inducing delay in cell cycle after MMC treatment may not be relevant for SCE-induction.

Interaction of radiation- and bleomycin-induced lesions and influence of glutathione level on the interaction

Abstract: Radiation-induced exchange aberrations are thought to arise as a consequence of misrejoining of free ends of DNA double strand breaks (dsbs). In quiescent mammalian cells this process of misrejoining is prevalently taken up by the non-homologous end joining (NHEJ) process. In order to investigate the role of glutathione (GSH) in DNA dsb rejoining, the interaction of the lesions induced by bleomycin (Blem) and by radiation was studied since the lesions caused by both have similar and apparent rapid rates of repair. Endogenous GSH was depleted by buthionine sulfoximine (BSO) and chromosome aberrations (CAs) of human lymphocytes were scored from first cycle metaphases. Gamma radiation was administered 2 h after Blem treatment in combined studies. In the case of BSO, the treatment was given 3 h before Blem treatment. The BSO-treated samples showed higher sensitivity to radiation than BSO-untreated ones. Combined treatment of Blem and radiation induced higher frequency of CAs, in particular the exchange aberrations and interstitial deletions. However, such increased frequency of exchange aberrations was reduced drastically and the frequency of terminal deletions was increased significantly when combined treatment was given to BSO-pretreated cells. The consistent level of Ku70 protein in all the treated samples, with undetectable level of Rad51 in the G 0 -lymphocytes indicates the involvement of NHEJ pathway in misrejoining of DNA dsbs. It may be hypothesized that reduction in the frequency of exchange aberrations as induced by Blem + radiation combined treatment in BSO-treated samples could be because of reduced NHEJ pathway.

Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice

Abstract: Insulin-like growth factor-1 (IGF-1), a key mediator of growth hormone action in mammals, plays an important role in the regulation of cellular and tissue functions. In the present investigation, the normal age-dependent and effect of dietary restriction on the expression levels of serum IGF-1, phosphotidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt) in the liver, kidney and skeletal muscles of 1-, 9-, and 21-month-old female mice were ascertained using ELISA and Western blot analysis. Results showed that serum IGF-1 peaks at 9-month-old and decreases in older age. Dietary restriction (DR) decreases IGF-1 in both age groups. In liver, PI3K and relative amount of phosphorylated Akt (pAkt/Akt) showed an age-dependent correlated expression level as IGF-1 protein. In kidney and skeletal muscles, PI3K levels showed no changes with age. However, pAkt/Akt ratio increased in 9-month-old mice and decreased in 21-month-old mice. In liver, DR increased the level of PI3K and pAkt/Akt ratio in 9-month-old mice, but no significant change was seen in 21-month-old mice as compared to ad libitum-fed group. In kidney and skeletal muscles, DR mice showed an increase in PI3K level in both age groups while the pAkt/Akt ratio showed no change in 9-month-old mice, but exhibited a decrease in 21-month-old mice. These results indicate that there is a tissue-specific regulation of IGF-1/PI3K/Akt during normal aging and upon DR to help maintain the metabolic status of these tissues at those phases of animal's lifespan.