PCB congener specific oxidative stress response by microarray analysis using human liver cell line

In this study we have examined the effect of exposure to different congeners of PCBs and their role in oxidative stress response. A metabolically competent human liver cell line (HepG2) was exposed with two prototype congeners of PCBs: coplanar PCB-77 and non-coplanar PCB-153. After the predetermined times of exposure (0–24 h) at 70 μM concentration, the HepG2 cells showed significant apoptotic changes by fluorescent microscopy after 12 h of exposure. Gene set enrichment analysis (GSEA) identified oxidative stress as the predominant enrichment. Further, paraquat assay showed that PCB congeners lead to oxidative stress to different extents, PCB-77 being more toxic. This study, with emphasis on all recommended microarray quality control steps, showed that apoptosis was one of the most significant cellular processes as a result of oxidative stress, but each of these congeners had a unique signature gene expression, which was further validated by Taqman real time PCR and immunoblotting. The pathways involved leading to the common apoptotic effect were completely different. Further in-silico analysis showed that PCB-153 most likely acted through the TNF receptor, leading to oxidative stress involving metallothionein gene families, and causing apoptosis mainly by the Fas receptor signaling pathway. In contrast, PCB-77 acted through the aryl hydrocarbon receptor. It induced oxidative stress through the involvement of cytochrome P450 (CYP1A1) leading to apoptosis through AHR/ARNT pathway.     

Induction of sperm impairments in mice as a sensitive biomarker of arsenic toxicity

The ubiquitous presence of arsenic (a toxic metalloid) in our environment, particularly in our drinking water, is a serious health hazard of global concern. The present work deals with the assessment of arsenic toxicity through the analysis of induced sperm impairments in sperm head morphology and sperm count in mice at low exposures compared to the magnitude of response at high exposure levels. The animals were exposed to four doses of arsenic, ranging from lowest dose of 0.3 μg kg^?1 day^?1 (the human reference dose) to higher dose of 30 μg kg^?1 day^?1 for 15 consecutive days. The epididymal sperms were harvested after one spermatogenic cycle on the 36th day and were scored for the presence of any abnormality in their head morphology as well as changes in their count. Exposure to arsenic significantly induced, in a dose-dependent manner, increases in the frequency of sperms with abnormal head morphology from 5.12 % in control to 9.23 % in lowest dose group and 23.02 % in highest dose group. In contrast, the mean sperm counts in the epididymal wash were decreased from 6.05 million per milliliter in the control to 4.95 million per milliliter in the lowest dose group and 3.07 million in the highest dose group. The analysis of sperm impairments in mice was, therefore, found to be a highly sensitive assay to assess arsenic toxicity, exhibiting a marked male reprotoxic effect of arsenic even at its low exposure levels including the human reference dose.     

Unravelling the molecular mechanism of mutagenic factors impacting human health

Environmental Science and Pollution Research - Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate...     

Mutagenic factors in the environment impacting human and animal health

Environmental Science and Pollution Research -