Y. Suneetha

Lead acetate induced reproductive and paternal mediated developmental toxicity in rats

Lead was administered orally to adult male rats at exposure level of 273 or 819 mg/L (0.05% or 0.15% lead acetate, respectively) for 45 days via drinking water. At the end of the exposure period, control and experimental males were mated with untreated females. Of the females mated with treated males, 73.3% in the 0.05% group and 53.33% in the 0.15% group showed copulatory plugs. Significant decrease in number of implantations and pre- and post-implantation loss was also observed in females mated with treated males. Significant decrease in the weight of the reproductive organs, reduction in epididymal sperm count, motile sperm and viable sperm were observed in lead-exposed rats indicating decreased sperm production and deteriorated sperm quality. Significant decrease in serum testosterone levels were also observed in treated rats indicating decreased steroidogenesis. The decreased serum testosterone levels and deteriorated sperm quality might be responsible for the suppressed reproduction in rats after exposure to lead.

Molecular docking, QSAR and AMDET analysis of 6-methyl-1,3,8-trichlorodibenzofuran and its analogs against Estrogen receptor alpha

Estrogen receptor alpha (ERα) plays a key role in the malignancy of breast cancer. Therefore, inhibitors for ERα can act as useful agents for the treatment of breast cancer. In the present study, we describe docking, toxicity prediction as a rational strategy for identification of novel hits or leads. Pubmed search showed, 76 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) analogs. Molecular docking of these analogs and MCDF against human estrogen receptor alpha ligand-binding domain showed 48 compounds containing binding energy greater than MCDF. Further, in silico pharmacological and structural studies were successful in predicting two compounds 4,6-dichloro-2-methyl-1-benzofuran (CID 57722561) and 1-chlorodibenzofuran (CID 55293) as inhibitors against Estrogen receptor alpha.

Prediction and Analysis of Breast Cancer Related Deleterious Non-Synonymous Single Nucleotide Polymorphisms in the PTEN Gene

One of the most common cancer types faced by the women around the world is breast cancer. Among the several low, moderate and high penetrance genes conferring susceptibility to breast cancer, PTEN is one which is known to be mutated in many tumor types. In this study, we predicted and analyzed the impact of three deleterious coding non-synonymous single nucleotide polymorphisms rs121909218 (G129E), rs121909229 (R130Q) and rs57374291 (D107N) in the PTEN gene on the phenotype of breast tumors using computational tools SIFT, Polyphen-2, PROVEAN, MUPro, POPMusic and the GETAREA server.

Structural effect of P278A mutation conferring breast cancer susceptibility in the p53 DNA-binding core domain

One of the common malignancies faced by womenaround the world is breast cancer. Risk factors for breastcancer include both genetic and non-genetic. Variants insome of the candidate genes are a common risk factor inbreast cancer. These genetic variants associated withbreast cancer can be classified as high, moderate or lowbased on relative risk [1]. Among them, genes that pre-dispose to high risk for breast cancer include TP53 ,BRCA1 ,BRCA2 ,PTEN ,STK11 and CDH1. A large num-ber of studies have assessed the prognostic and predictiverole of TP53 alterations in breast cancer. It is well knownthat TP53 is mutated in about 30% of breast cancers [2].We have analyzed the genetic variation that may alter theexpression and function of the TP53 gene using thesequence-homology-based SIFT tool [3] and a structure-based approach using the PolyPhen-2 server [4]. Thesetwo computational approaches showed that rs17849781(P278A) has a deleterious phenotypic effect conferring tobreast cancer. Further, we have analyzed the structuraleffect of the P278A mutation in the p53 DNA-bindingcore domain by employing different computationalmethods.