Current R&D Activities:
R&D activities have been directed to identify the role of xenobiotic metabolizing cytochrome P450s in tissue specific toxicity with emphasis on the following: 

Expression of cytochrome P450s in brain and their role in neurobehavioral toxicity of pesticides: 
Major interest in the basic research has been directed to identify and distinguish the xenobiotic metabolizing cytochrome P450s (CYPs) in brain. Studies include identification of the different gene families of CYPs in brain, understanding of their substrate specificity, overlapping substrate specificity with the endogenous substances affecting cerebral functions and their role in neurotoxicity of drugs and environmental chemicals. Our studies provided evidence for the expression of xenobiotic metabolizing cytochrome P450 1A1 (CYP1A1), 1A2, CYP2B1, 2B2, CY2E1 and CYP3A isoenzymes in rat brain and brain regions. Lindane, an organ chlorine insecticide, and deltamethrin, a pyrethroid insecticide was found to modulate the expression of xenobiotic metabolizing CYPs in rat brain. Induction studies further demonstrated the involvement of CYPs in the neurobehavioral toxicity of these pesticides. 

Our data further revealed relatively higher expression of xenobiotic metabolizing CYP1A-, CYP2B- and CYP2E1 in cultured rat brain neuronal cells when compared to the glial cells. Responsiveness of cultured neuronal and glial CYPs have suggested that CYPs may not only have a potential role in the toxication-detoxication mechanism but may be associated with alteration in specific neurotransmitter pathways and intricate signaling mechanisms in brain. 

Blood cytochrome P450 (CYPs) expression profiles as biomarker of chemical exposure and effect: 
Regulation of xenobiotic metabolizing CYPs was studied in freshly isolated rat blood lymphocytes for generating CYP expression profile in blood lymphocytes as a sensitive and mechanistic based biomarker of chemical exposure. Significant mRNA and protein expression of xenobiotic metabolizing CYPs in rat blood lymphocytes and similarities in the regulation of catalytic activity of these CYPs in blood lymphocytes with that of liver enzymes suggest that blood CYPs can be used as a surrogate to monitor hepatic changes of these enzymes. 

Predictive toxicology and single nucleotide polymorphism (SNPs):
The information on the individuals that are in high-risk category because of their genetic predisposition, will be helpful in protecting them from the harmful effects of environmental toxicants as well as adverse drug effects. Studies initiated in a CSIR network program coordinated by IGIB, N. Delhi to identify SNPs in the enzymes (CYPs, GSTs, oxidative stress enzymes etc) involved in xenobiotic metabolism and toxicity in the Indian population revealed the presence of several of the SNPs in these genes in representative samples of Indian populations. 

In a case-control study, association of SNPs in phase-I and phase-II enzymes and those involved in neurotransmission is being investigated with environment induced diseases such as head and neck cancer (HNSCC), lung cancer, alcoholic liver cirrhosis and Parkinson disease (PD). Our data suggest gene-gene and gene-environment interaction in modifying the susceptibility to HNSCC and lung cancer. Likewise, our study, currently in progress, suggest that combination of multiple genotypic risk factors, responsive to environmental exposures, may possibly lead to the development of biomarkers that may help in tracking the initiation and progression of Parkinson disease.