Study of genetic polymorphism in solvent exposed population and its correlation to in vitro effect of trichloroethylene on lymphocytes.
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 maybe toxic due to its metabolite.
Kumar
Munish
M
Petroleum Toxicology Division, Indian Institute of Toxicology Research, Lucknow-226 001, India.
Tewari
Shikha
S
Sharma
Priti
P
Verma
Vipin Kumar
VK
Chauhan
L K S
LK
Agarwal
Sudhir Kumar
SK
Dwivedi
U N
UN
Goel
Sudhir Kumar
SK
D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000737:chemistry / Q000235:genetics; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007194:India; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D016273:Occupational Exposure; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000187:drug effects*; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D014241:Trichloroethylene / Q000633:toxicity*
D019363:Cytochrome P-450 CYP1A1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D014241:Trichloroethylene; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human