title: Increase in intracellular Ca(2+) level by phenylsulfamide fungicides, tolylfluanid and dichlofluanid, in rat thymic lymphocytes.
abstract: Tolylfluanid, a phenylsulfamide fungicide, is one of the many pesticides that are frequently detected in crops. Therefore, its health risk is a concern. Micromolar concentrations of tolylfluanid induce chromosomal aberrations and micronuclei in mammalian lymphocytes. The findings prompted us to study the cellular actions of tolylfluanid and another frequently detected pesticide, dichlofluanid, at submicromolar and micromolar concentrations. Of the cellular actions of chemicals, the action on cellular Ca(2+) homeostasis is important since Ca(2+) is involved in cell signaling and death. Consequently, in this study, the effects of phenylsulfamide fungicides were examined on rat thymocytes by using fluorescent probes in order to further characterize the cellular actions of phenylsulfamide fungicides. Both phenylsulfamide fungicides exhibited biphasic, early and late, increase in intracellular Ca(2+) levels. The early phase was dependent on intracellular Ca(2+) release and increased membrane Ca(2+) permeability. The late phase was owing to Ca(2+) influx via activation of store-operated Ca(2+) channels and the further increase of membrane ionic permeability. Voltage-dependent Ca(2+) channels were not involved. The increases in intracellular Ca(2+) levels by phenylsulfamide fungicides were observed at drug concentrations of 0.1 μM or more (up to 10 μM). Thus, it is plausible that micromolar concentrations of phenylsulfamide fungicides deregulate intracellular Ca(2+) homeostasis in rat thymocytes. Both phenylsulfamide fungicides at 10 μM promoted the transition from intact living cells to living cells with phosphatidylserine-exposed membranes. This was not the case for phenylsulfamide fungicides at 3 μM. The potency of tolylfluanid was similar to that of dichlofluanid. Although the information on residual concentrations of tolylfluanid and dichlofluanid is very limited, their residual concentrations do not reach micromolar levels. It is unlikely that humans will develop adverse effects on exposure to phenylsulfamide fungicides under present environmental conditions.
authors.affiliation: Graduate School of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Fukunaga
authors.affiliation: Graduate School of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Enma
authors.affiliation: Graduate School of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 734-8553, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nishimura-Danjyobara
authors.affiliation: Graduate School of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan. Electronic address: oyamay@tokushima-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oyama
authors.affiliation: Kumamoto Health Science University, Kumamoto 861-5598, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005659:Fungicides, Industrial / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013449:Sulfonamides / Q000633:toxicity*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014052:Toluidines / Q000633:toxicity*
chemical_list: D000814:Aniline Compounds; D005659:Fungicides, Industrial; D013449:Sulfonamides; D014052:Toluidines; C070021:N-dichlorofluoromethylthio-N',N'-dimethyl-N-p-tolylsulfamide; C016370:dichlofluanid; D002118:Calcium
keywords: Cytotoxicity; Dichlofluanid; Intracellular Ca(2+); Lymphocyte; Tolylfluanid