Journal of Environmental Biology

Study of genetic polymorphism in solvent exposed population and its

correlation to in vitro effect of trichloroethylene on lymphocytes

 

Munish Kumar¹, Shikha Tewari¹, Priti Sharma¹, Vipin Kumar Verma¹, L.K.S. Chauhan²,

Sudhir Kumar Agarwal³, U.N. Dwivedi³ and Sudhir Kumar Goel*¹

 

¹Petroleum Toxicology Division, ²Cell Biology Section, Indian Institute of Toxicology Research, Lucknow - 226 001, India

³Department of Biochemistry, Lucknow University, Lucknow - 226 007, India

 

(Received: May 09, 2008; Revised received: September 17, 2008; Accepted: September 30, 2008)

 

Abstract: Trichloroethylene (TCE) is major industrial pollutant that contaminate environment. Its exposure may lead to hepato-renal toxicity along with the cancer progression. Although extensive research is done on its toxicity, still not much is known about its genotoxic potential on humans in relation to genetic polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs) are important in cellular detoxification of TCE. Variations in gene sequences result in population specific regional genetic variations (polymorphism). Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220 normal and 97 solvent-exposed individuals from northern part of India using real time PCR, PCR and restriction digestion techniques. The parameters examined to study genotoxicity were chromosomal aberration (CA) and cytokinesis block micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or (ile/val) or (val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9% respectively. It was further observed that the frequencies of above genes were found to be similar in solvent exposed groups. The distribution frequencies of GST genes, when compared with other reports from various regions of India show variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant genotoxic effect.? TCE may be toxic due to its metabolite.

Key words: Genotoxicity, TCE, Lymphocytes, CYP1A1, GSTP1, Real time PCR

 

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