Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches.

Trichloroethylene (TCE) is a ubiquitous environmental contaminant, which may have effects on both ecosystem and human health. TCE has been reported to cause several toxic effects, but little effort has been made to assess the ecological risks of TCE or its major metabolites: trichloroethanol (TCOH), trichloroacetic acid, and oxalic acid (OA). In this study, the endocrine-disrupting potential of TCE and its metabolites were investigated using in vitro and in silico approaches. We examined alterations in the steroidogenesis pathway using the NCI-H295R cell line and utilized receptor-mediated luciferase reporter cell lines to identify effects on estrogen and androgen receptors. Molecular docking was also used to explore chemical interactions with these receptors. All test chemicals except OA significantly increased 17ß-estradiol production which can be attributed to an up-regulation of 17ß-hydroxysteroid dehydrogenase. Moreover, TCOH exhibited significant antiestrogenic activity with a RIC20 (20% relative inhibitory concentration) of 3.7 × 10-7 M. Molecular docking simulation supported this finding with lower docking scores for TCOH, indicating that hydrogen bonds may stabilize the interaction between TCOH and the estrogen receptor binding pocket. These findings suggest that TCE contamination poses an endocrine-disrupting threat, which has implications for both ecological and human health.

Experimental Evidence for Noncanonical Thymine Cation Radicals in the Gas Phase.

Thymine cation radicals were generated in the gas phase by collision-induced intramolecular electron transfer in [Cu(2,2':6,2″-terpyridine)(thymine)]2+• complexes and characterized by ion-molecule reactions, UV-vis photodissociation action spectroscopy, and ab initio and density functional theory calculations. The experimental results indicated the formation of a tautomer mixture consisting chiefly (77%) of noncanonical tautomers with a C-7-H2 group. The canonical 2,4-dioxo-N-1,N-3-H isomer was formed as a minor component at ca. 23%. Ab initio CCSD(T) calculations indicated that the canonical [thymine]+• ion was not the lowest-energy isomer. This contrasts with neutral thymine, for which the canonical isomer is the lowest-energy structure. Exothermic unimolecular isomerization by a methyl hydrogen migration in the canonical [thymine]+• ion required a low energy barrier, forming a C-7-H2,O-4-H isomer. Noncanonical thymine tautomers with a C-7-H2 group were also identified by calculations as low-energy isomers of 2'-deoxythymidine phosphate cation radicals. The relative energies of thymidine ion isomers were sensitive to the computational method used and were affected by solvation. The noncanonical [thymine]+• ions have extremely low adiabatic recombination energies (REadiab < 5.9 eV), making them potential ionization hole traps in ionized nucleic acids.