title: Micronucleus induction by oxidative metabolites of trichloroethylene in cultured human peripheral blood lymphocytes: a comparative genotoxicity study.
abstract: The genotoxic effects of oxidative metabolites of trichloroethylene (TCE), namely chloral hydrate, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCEOH) were examined in human peripheral blood lymphocytes. In this context, lymphocytes were exposed in vitro to 25, 50, and 100 μg/ml concentrations of these metabolites separately for a period of 48 h and examined for micronucleus (MN) induction through flow cytometer. At 50 μg/ml TCE metabolites, TCA (6.33 ± 0.56 %), DCA (5.06 ± 0.55), and TCEOH (4.70 ± 1.73) induced highly significant (p<0.001) frequency of MN in comparison to control (1.03 ± 0.40) suggestive of their genotoxic potential. However, exposure of 100 μg/ml of all the metabolites consistently declined the frequencies of MN which in some cases was equable to that of observed at 25 μg/ml. Further, cytotoxicity and cell cycle disturbances were also measured to find out the association of these endpoints with the MN induction. DNA content analysis revealed 3-4-fold elevation of S-phase at all the concentrations tested. Particularly, at 100 μg/ml, treatment elevation of S-phase was significantly (p<0.0001) higher as compared to the control. Present findings together with earlier reports indicate that TCE induces genotoxicity through its metabolites. Interaction of these metabolites with DNA, as evident by elevated S-phase, seems to be the major cause of MN induction. However, involvement of spindle disruption cannot be ruled out. This comparative study also suggests that after TCE exposure, the metabolic efficiency of human to generate oxidative metabolites determines the extent of genotoxicity.
authors.affiliation: Petroleum Toxicology Division, Indian Institute of Toxicology Research (IITR), Council of Scientific and Industrial Research, P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow, 226001, India.
authors.forename: Meenu
authors.initials: M
authors.lastname: Varshney
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chandra
authors.forename: L K S
authors.initials: LK
authors.lastname: Chauhan
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Goel
mesh_terms: D002478:Cells, Cultured; D004249:DNA Damage; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010084:Oxidation-Reduction; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D015386:Hazardous Substances; D009153:Mutagens; D014241:Trichloroethylene; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol