PMID- 20920556 OWN - NLM STAT- MEDLINE DCOM- 20101217 LR - 20131121 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 199 IP - 3 DP - 2010 Dec 15 TI - Prior exposure to organophosphorus and organochlorine pesticides increases the allergic potential of environmental chemical allergens in a local lymph node assay. PG - 347-56 LID - 10.1016/j.toxlet.2010.09.018 [doi] AB - The dysregulation of immune functions by some pesticides leads to various immune disorders, including immunodeficiency, tumorigenesis, allergies, and autoimmunity. This study's primary objective was to examine the relationship between immune disorders and the immunosuppression induced by immunosuppressive pesticides. We focused on the modulation of allergic potential by the organophosphorus pesticide parathion, organochlorine pesticide methoxychlor, phenoxyacetic acid herbicide 2,4-d-butyl, and benzoic acid fungicide eugenol, as detected by a local lymph node assay (LLNA), which was developed initially for hazard identification of skin sensitization. Parathion and methoxychlor are immunosuppressive chemicals, and 2,4-d-butyl and eugenol are contact allergens. After the immunosuppressive characteristics of parathion and methoxychlor were confirmed in a pilot study, 4-week-old mice were orally administered parathion (0, 0.4, 1.2mg/kg) or methoxychlor (0, 100, 300 mg/kg). Four weeks after the last administration, an LLNA was conducted using 2,4-d-butyl (0%, 2.5%, 5%, and 10%) and eugenol (0%, 5%, 10%, and 25%). In addition, detailed analysis of their auricular lymph nodes for number of surface antigen expression of T cells and local cytokine production were performed using 5% 2,4-d-butyl and 5% eugenol treatment groups. EC3 values (estimated concentration to yield a stimulation index of 3) of 2,4-d-butyl and eugenol decreased markedly in parathion- and methoxychlor-pretreated groups. Parathion- and methoxychlor-pretreated groups induced marked increase in number of surface antigen expression of T cells and levels of Th1 cytokines (IFN-gamma, TNF-alpha, and IL-17) produced by ex vivo restimulated lymph node cells. According to our results, the allergic potentials of 2,4-d-butyl and eugenol are increased by prior exposure to parathion and methoxychlor. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Fukuyama, Tomoki AU - Fukuyama T AD - Institute of Environmental Toxicology, Ibaraki 303-0043, Japan. fukuyama@iet.or.jp FAU - Kosaka, Tadashi AU - Kosaka T FAU - Tajima, Yukari AU - Tajima Y FAU - Ueda, Hideo AU - Ueda H FAU - Hayashi, Koichi AU - Hayashi K FAU - Shutoh, Yasufumi AU - Shutoh Y FAU - Harada, Takanori AU - Harada T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Allergens) RN - 0 (Cytokines) RN - 0 (Pesticides) RN - 2577AQ9262 (2,4-Dichlorophenoxyacetic Acid) RN - 3T8H1794QW (Eugenol) RN - 61G466064D (Parathion) RN - 94-80-4 (2,4-D n-butyl ester) RN - RIA79UD69L (Methoxychlor) SB - IM MH - 2,4-Dichlorophenoxyacetic Acid/*analogs & derivatives/immunology MH - Allergens/*immunology MH - Animals MH - Cytokines/biosynthesis MH - Dose-Response Relationship, Drug MH - Eugenol/*immunology MH - Female MH - Methoxychlor/*toxicity MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred CBA MH - Parathion/*toxicity MH - Pesticides/*toxicity EDAT- 2010/10/06 06:00 MHDA- 2010/12/18 06:00 CRDT- 2010/10/06 06:00 PHST- 2010/08/30 00:00 [received] PHST- 2010/09/23 00:00 [revised] PHST- 2010/09/24 00:00 [accepted] PHST- 2010/10/06 06:00 [entrez] PHST- 2010/10/06 06:00 [pubmed] PHST- 2010/12/18 06:00 [medline] AID - S0378-4274(10)01706-6 [pii] AID - 10.1016/j.toxlet.2010.09.018 [doi] PST - ppublish SO - Toxicol Lett. 2010 Dec 15;199(3):347-56. doi: 10.1016/j.toxlet.2010.09.018.