Mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes
Authors: Javed Musarrat
Kulpreet Bhui
Abdulaziz A Al-Khedhairy
Pramod Kumar Srivastava
Shilpa Tyagi
Wahid Ali
Amit Kumar Srivastava
Yogeshwer Shukla
Richa Singh
Journal: Life Sciences (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mancozeb; genotoxicity; apoptosis; lymphocytes; chromosomal aberrations
Affiliations: Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow, UP 226001, India.

Abstract:  Aims: Mancozeb is a dithiocarbamate fungicide known to be genotoxic and induces tumors in rodents at various sites. There is no report in the literature about its genotoxicity in humans. Here, we investigated the association between mancozeb exposure and induction of genotoxic and proapoptotic changes in cultured human lymphocytes (CHLs). Main methods: Lymphocytes were isolated from peripheral blood of healthy non-smoking donors. Induction of micronuclei and chromosomal aberrations was recorded both by conventional and flow cytometric methods. Annexin-V FITC was used for the differentiation of apoptotic and necrotic cells by flow cytometry. Key findings: Mancozeb exposure (0.5, 2 and 5 μg/ml) to CHLs leads to significant induction in the frequency of chromosomal aberrations (CAs) and micronuclei (MN), in a dose-dependent manner. Concomitantly, pro-oxidant potential of mancozeb was also recorded, by increase in the levels of reactive oxygen species (ROS) generation. Our results demonstrated that ROS plays a critical role in the initiation of mancozeb induced apoptosis in CHLs through two ways, primarily through mitochondria-mediated pathway including induction of ROS, decrease in mitochondrial membrane potential (ΔΨm), along with cytochrome c release from mitochondria, and activation of the caspase cascade. The other pathway includes increase in ROS, which resulted in activation of NF-κB, expression of FasL and triggered FasL-dependent pathway, which also involves caspase-8. Therefore, exposure to mancozeb can lead to induction of apoptosis in CHLs through both mechanisms. Significance: The results of study confirm that mancozeb exposure can induce genotoxicity and apoptosis in CHLs, thus pose a potential risk to exposed human population. 

Retracted: No

PubPeer comments:
 Figure 2 showing manipulated dot plots for two different treatment groups. ![file] , 
 Figure 6 (caspase 9 blot) is more similar than one would expect with figure 5 (total ERK1 2) of a previous paper from this group. The same blot with two different exposures appears to have been used after changing the orientation as illustrated below. ![file] , 
  Fig. 4. Effect of mancozeb on induction of apoptosis in CHLs:... (c) Apoptotic effect was assessed by DNA fragmentation assay using (0.8%) agarose gel electrophoresis. Control cells showing no ladder formation or single band of DNA (lane 2) while ladders were observed in 0.5, 2 and 5 u03bcg ml mancozeb exposed cells (lanes 3, 4 and 5. Marker was run in lane 1). Lanes 4 and 5 are identical for most of their lengths, with only cosmetic changes along the edges of the upper half. ![file] , 
 Hoya: your claim is tenuous , 
 #2 Comparing another panel from Figure 6 (lower right) with one from Fig 2(a) of [George et al. (2011)] (at lower left). ![file] , 
 #1  Figure 2 showing manipulated dot plots for two different treatment groups I do not know if this comment really captures the **extent** of the manipulation. ![file] , 
 Retracted [6 August 2022] . ------------------------ This article has been retracted at the request of the Editor-in-Chief. Multiple figures in this article appear to be falsified fabricated. Figure 2 shows manipulated dot plots for two different treatment groups (2u03bcl ml and 5u03bcl ml). Figure 6 (caspase 9 blot) is very similar to figure 5 (total ERK1 2) of a previous paper from this group published in Cancer Letters, 282, (2009) 67-176, https: doi.org 10.1016 j.canlet.2009.03.003. In Fig 4., Lanes 4 and 5 are identical for most of their lengths, with only cosmetic changes along the edges of the upper half. Figure 6 contains similar portions of Fig 2(a) of a paper published by the same group in Food and Chemical Toxicology, 49, (2011) 1511-1520, https: doi.org 10.1016 j.fct.2011.03.040 The authors have not been able to provide any justification for this image manipulation. ,