title: In vitro investigations for the QSAR mechanism of lymphocytes apoptosis induced by substituted aromatic toxicants.
abstract: The objective of this study was to assess the chemicals-induced apoptosis effects on fish lymphocytes and to use the QSAR model to interpret the relationships between apoptotic effects and chemical structures to identify the immune toxicology mechanism. By the use of a simple in vitro toxicological assay, the measured apoptotic parameter (EC50) is used in a QSAR to interpret the apoptotic effects of 25 substituted benzenes at low exposure levels. The apoptotic effects of all tested substituted aromatic chemicals with Carassius auratus lymphocytes were confirmed by DNA ladder and nucleus condensation. For both chlorobenzenes and PCBs, the EC50 values increase with increasing Cl number in the molecule, a result reflecting probably the increased p-pi conjugation of the C-Cl bonds that lowers the molecular reactivity. Furthermore, the apoptotic EC50 data were best correlated with the dipole moment (mu) and the energy of the lowest unoccupied molecular orbital (ELUMO) such that: log(1/EC50)=0.325+0.222 micro-0.163(ELUMO) (with R(2)=0.879). The dependence on the electronic ELUMO factor of the established correlation suggests that during the apoptotic process the ROS (reactive oxygen substance) produced by cells acts as a Lewis base in substituted nucleophilic reactions with toxic chemicals behaving as an electron acceptor. On the basis of the test results, the present toxicological assay offers a rapid tool for assessing the toxic effects of chemicals at low exposure levels.
authors.affiliation: College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310028, People's Republic of China.
authors.forename: Hangjun
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001555:Benzene Derivatives / Q000737:chemistry* / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D006054:Goldfish; D016014:Linear Models; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
chemical_list: D001555:Benzene Derivatives; D004247:DNA