title: Apoptosis in immunocytes induced by several types of pesticides.
abstract: Several types of pesticides, such as organophosphates and organochlorines, can induce thymocyte apoptosis, resulting in thymic atrophy and predisposing the highly sensitive fetal immune system to loss of tolerance to self-antigens and subsequent increased risk for autoimmune disease and allergies. In the studies here, mouse primary thymocytes and a human acute T-cell leukemia cell line (J45.01) were employed to examine potential thymocyte apoptosis induced by several types of chemicals, including several commonly-used pesticides. Thymocytes and J45.01 cells were treated for 4 or 8 hr with varying doses of metamidophos, parathion, PNMC, or methoxychlor; dexamethasone was used as a positive control. Apoptosis, cell viability, the proportion of Annexin-V+ cells, the activities of caspases 3/7, 8, and 9, and the levels of DNA fragmentation in both the J45.01 cells and thymocytes were then examined. The results here show that with both cell types, there was an increase in the proportion of annexin-V+ cells and levels of DNA fragmentation following exposure to parathion, PNMC, methoxychlor, or dexamethasone (positive control); however, the levels of sensitivity appeared to differ between the cell types. Furthermore, caspase-7 and -8 activities also differed between the J45.01 cells and thymocytes when treated with PNMC, methoxychlor, or dexamethasone. A more precise characterization of these inter-cellular differences is the logical next step in our studies of the effects of these (and other) pesticides on immune cell integrity. These specific types of follow-on mechanistic experiments are currently underway in our laboratories.
authors.affiliation: Institute of Environmental Toxicology, Ibaraki, Japan. fukuyama@iet.or.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tajima
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Shutoh
authors.forename: Takanori
authors.initials: T
authors.lastname: Harada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kosaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010575:Pesticides / Q000633:toxicity*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D010575:Pesticides