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Title: DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism

Abstract

The DNA damaging and proapoptotic effects of Mancozeb, a widely used fungicide of the ethylene-bis-dithiocarbamate (EBDC) group, were studied in RAT-1 fibroblasts cultured in vitro and in peripheral blood mononucleated cells (PBMC) isolated from Wistar rats. After 1 h exposition to Mancozeb (up to 500 ng/ml), cells produced a dose-dependent induction in DNA single strand break (SSB) formation, measured by single cell gel electrophoresis (SCGE). Concomitantly, a concentration-dependent increase in the levels of the oxidative markers of DNA oxidation, the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) and of reactive oxygen species (ROS) were observed, suggesting a prooxidant action of Mancozeb. PBMC were less responsive than fibroblasts to the oxidative insult carried out by Mancozeb, as shown by the lower increase in the levels of ROS, 8-OHdG adducts and SSB measured in these cells after exposure to the pesticide. A 4-h treatment with Mancozeb induced also apoptosis in both PBMC and RAT-1 cells, even though leukocytes were less sensitive than fibroblasts to the proapoptotic action. This effect was dose-dependent and was inhibited by the action of the antioxidant {alpha}-tocopherol. The proapoptotic effect was accompanied by the altered expression of several proteins involved in the regulation of apoptosis, such as the prosurvival protein BCL-2more » and the proapoptotic protein c-MYC. Exposition of cells to higher concentrations of Mancozeb or for longer periods (>4 h) caused post-apoptotic, necrotic alterations in cell membrane integrity. The data herein presented demonstrate the oxidative effect of Mancozeb and suggest that its prooxidant action may be involved in the proapoptotic effect exerted by this compound in rat cells. It appears possible that the observed oxidative and genotoxic damage may be involved in the pathogenesis of various pathologies associated with the chronic exposition to Mancozeb, including cancer. On the other hand, the proapoptotic effect of Mancozeb suggests its possible relevance in the pathogenesis of neurodegenerative diseases, often related to the exposition of pesticides.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1]
  1. Institute of General Pathology, Catholic University-L.go F. Vito, 1-00168 Rome (Italy)
  2. Institute of Pathology, Catholic University-L.go F. Vito, 1-00168 Rome (Italy)
Publication Date:
OSTI Identifier:
20783432
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 211; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.06.001; PII: S0041-008X(05)00364-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; BORON CHLORIDES; CELL MEMBRANES; DNA; ELECTROPHORESIS; ETHYLENE; FIBROBLASTS; FUNGICIDES; GELS; HYDROGEN 4; IN VITRO; LEUKOCYTES; NEOPLASMS; NERVOUS SYSTEM DISEASES; OXIDATION; PATHOGENESIS; PATHOLOGY; PROTEINS; RATS; STRAND BREAKS; VITAMIN E

Citation Formats

Calviello, Gabriella, Piccioni, Elisabetta, Boninsegna, Alma, Tedesco, Beatrice, Maggiano, Nicola, Serini, Simona, Wolf, Federica I, and Palozza, Paola. DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.06.001.
Calviello, Gabriella, Piccioni, Elisabetta, Boninsegna, Alma, Tedesco, Beatrice, Maggiano, Nicola, Serini, Simona, Wolf, Federica I, & Palozza, Paola. DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism. United States. https://doi.org/10.1016/j.taap.2005.06.001
Calviello, Gabriella, Piccioni, Elisabetta, Boninsegna, Alma, Tedesco, Beatrice, Maggiano, Nicola, Serini, Simona, Wolf, Federica I, and Palozza, Paola. 2006. "DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism". United States. https://doi.org/10.1016/j.taap.2005.06.001.
@article{osti_20783432,
title = {DNA damage and apoptosis induction by the pesticide Mancozeb in rat cells: Involvement of the oxidative mechanism},
author = {Calviello, Gabriella and Piccioni, Elisabetta and Boninsegna, Alma and Tedesco, Beatrice and Maggiano, Nicola and Serini, Simona and Wolf, Federica I and Palozza, Paola},
abstractNote = {The DNA damaging and proapoptotic effects of Mancozeb, a widely used fungicide of the ethylene-bis-dithiocarbamate (EBDC) group, were studied in RAT-1 fibroblasts cultured in vitro and in peripheral blood mononucleated cells (PBMC) isolated from Wistar rats. After 1 h exposition to Mancozeb (up to 500 ng/ml), cells produced a dose-dependent induction in DNA single strand break (SSB) formation, measured by single cell gel electrophoresis (SCGE). Concomitantly, a concentration-dependent increase in the levels of the oxidative markers of DNA oxidation, the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) and of reactive oxygen species (ROS) were observed, suggesting a prooxidant action of Mancozeb. PBMC were less responsive than fibroblasts to the oxidative insult carried out by Mancozeb, as shown by the lower increase in the levels of ROS, 8-OHdG adducts and SSB measured in these cells after exposure to the pesticide. A 4-h treatment with Mancozeb induced also apoptosis in both PBMC and RAT-1 cells, even though leukocytes were less sensitive than fibroblasts to the proapoptotic action. This effect was dose-dependent and was inhibited by the action of the antioxidant {alpha}-tocopherol. The proapoptotic effect was accompanied by the altered expression of several proteins involved in the regulation of apoptosis, such as the prosurvival protein BCL-2 and the proapoptotic protein c-MYC. Exposition of cells to higher concentrations of Mancozeb or for longer periods (>4 h) caused post-apoptotic, necrotic alterations in cell membrane integrity. The data herein presented demonstrate the oxidative effect of Mancozeb and suggest that its prooxidant action may be involved in the proapoptotic effect exerted by this compound in rat cells. It appears possible that the observed oxidative and genotoxic damage may be involved in the pathogenesis of various pathologies associated with the chronic exposition to Mancozeb, including cancer. On the other hand, the proapoptotic effect of Mancozeb suggests its possible relevance in the pathogenesis of neurodegenerative diseases, often related to the exposition of pesticides.},
doi = {10.1016/j.taap.2005.06.001},
url = {https://www.osti.gov/biblio/20783432}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 211,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2006},
month = {Wed Mar 01 00:00:00 EST 2006}
}