Genotoxicity and immunotoxic effects of 1,2-dichloroethane in Wistar rats

Abstract

Dichloroethane is widely used as a solvent, degreasing agent and in a variety of commercial products, and is known for being a ubiquitous contaminant in the environment. Important sources principally include the emissions from industrial processes, improper consumption, storage, and disposal methods. In view of the fact that the mechanism of its genotoxicity has not been satisfactorily elucidated, the acute in vivo toxicological impact is assessed in Rattus norvegicus. A systematic investigation has been made involving the use of conventional methods along with molecular and flow cytometric approaches. The micronucleus and chromosomal aberration frequencies were significantly elevated in bone marrow cells exposed to three concentrations at multiple treatment durations indicating positive time- and dose-response relationships. The mitotic index significantly decreased in similar concentrations in contrast to normal control. Separate studies were performed on blood cells for comet assay. It revealed dichloroethane-induced DNA damage in all exposures readily explainable in a dose- and time-dependent manner. Recent molecular techniques were further employed using leukocytes for the cell apoptosis/cycle and mitochondrial membrane potential employing propidium iodide staining and rhodamine-123, respectively. The effect on mitochondrial membrane permeability, cell cycle phases, and the DNA damage was analyzed through flow cytometry. These indicators revealed dichloroethane treatment decreased the mitochondrial membrane potential, affected the cell cycle, and confirmed the DNA damage, leading to apoptosis of the cells of the immune system responsible for immunotoxic effects of dichloroethane on rat leukocytes.

Investigation of potential early key events and mode of action for 1,2‐dichloroethane‐induced mammary tumors in female rats

“…The apparent contradiction when compared with the clear increases with in vitro bacterial and mammalian mutagenicity and clastogenicity may simply be a function of dose to the target cell; exposure and subsequent DNA damage in vivo may not be sufficient to elicit a mutagenic response. In contrast to the previous publications, a recent study purports to show DCE-induced micronuclei following intraperitoneal injection of DCE (Lone et al, 2016); however, substantial methodological and apparent clerical errors confound the evaluation and applicability of this study. For example, there were several substantial deviations from the standard study conduct, as described in the OECD in vivo Micronucleus Test Guideline 474 (OECD, 2016).…”

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data

“…Furthermore, the development and testing of medicinal drugs and vaccines depend heavily on animal models 129 . Before choosing an animal model to study an infectious agent, the scientific team must first decide if there is enough ex vivo and in vitro data available to support conducting research into an animal model, if ethical issues are taken care of, and if the data obtained from animal work will contribute meaningfully to the body of scientific knowledge 130–132 . In addition, in selecting an animal model, the animal's innate vulnerability to the virus under investigation should be taken into account.…”

“… 129 Before choosing an animal model to study an infectious agent, the scientific team must first decide if there is enough ex vivo and in vitro data available to support conducting research into an animal model, if ethical issues are taken care of, and if the data obtained from animal work will contribute meaningfully to the body of scientific knowledge. 130 , 131 , 132 In addition, in selecting an animal model, the animal's innate vulnerability to the virus under investigation should be taken into account. Animal models with natural disease transmission pathways, pathogenesis, and clinical illness progression that closely resemble the original host (humans, for example) are frequently preferred, depending on the goals of the research.…”