Stereospecificity in the cytotoxic action of hexachlorocyclohexane isomers

Anup, Srivastava and Shivanandappa, T. (2010) Stereospecificity in the cytotoxic action of hexachlorocyclohexane isomers. Chemico-Biological Interactions, 183. 34-39.

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Abstract

Hexachlorocyclohexane (HCH) is a highly recalcitrant organochlorine insecticide known for its chronic toxicity. In spite of many isolated studies a clear mechanism of cytotoxic action of HCH and the structure– toxicity relationship of its isomers is not well understood. We have investigated the toxicity of HCH isomers and its mechanism in Ehrlich Ascites tumor (EAT) cells. Our studies show differential cytotoxicity of HCH isomers (�, �, �, and �), � isomer being most toxic and � the least. HCH-induced cell death was associated with induction of reactive oxygen species (ROS) formation, lipid peroxidation (LPO), and depletion of glutathione (GSH). The increase in oxidative stress was linked with increased NAD(P)H oxidase activity. HCH inhibited Na+,K+-ATPase, which could be involved in raising the intracellular calcium and increased Ca2+,Mg2+-ATPase activity. HCH lead to apoptotic as well as necrotic cell death as it was marked by increased caspase-3 activity and lactate dehydrogenase (LDH) leakage, respectively. Based on the results it is concluded that the HCH isomers inflict differential cytotoxicity which was highest by � and lowest by �. Further, this study demonstrates for the first time a clear link between Na+,K+-ATPase, i[Ca2+] level, and oxidative stress in HCH-induced cytotoxicity.

Item Type:	Article
Uncontrolled Keywords:	Hexachlorocyclohexane, Oxidative stress, Na+,K+-ATPase, Ca2+,Mg2+-ATPase, NADPH oxidase, Intracellular calcium
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 26 Pesticide Chemistry
Divisions:	Food Protectants and Infestation Control
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	08 Jun 2011 10:39
Last Modified:	28 Dec 2011 10:23
URI:	http://ir.cftri.res.in/id/eprint/10089

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