Abstract
Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.
Highlights
Ecological balance is the result of a mutual relationship between living creatures and their ecosystem: each organism, is capable of rapidly responding and adapting to external perturbations, maintaining a dynamic equilibrium with the surroundings
The non-genotoxic and indirect genotoxic effects of organochlorine pesticides are expressed through various intracellular events, ranging from hyperproliferation to the activation of oncogenic signaling pathways responsible for growth factor release and reactive oxygen species (ROS) production [22]
We examined the potential role of β-HCH in tumor initiation by performing experiments on a human normal bronchial epithelium cell line, BEAS-2B
Summary
Ecological balance is the result of a mutual relationship between living creatures and their ecosystem: each organism, is capable of rapidly responding and adapting to external perturbations, maintaining a dynamic equilibrium with the surroundings. The environmental presence of pesticides, industrial waste, exhaust gas, particulate matter, and other xenobiotic substances has been universally considered to be accountable for many pathological conditions, including cancer [1,2,3,4]. The correlation between synthetic chemicals and carcinogenesis was originally identified in the middle 1700s [5], but it was only in 1915 that Yamagiwa published the first experimental study on cancer pathogenesis in association with environmental contaminant exposure [6]. The International Agency for Research on Cancer (IARC) has so far classified 120 agents as carcinogenic to humans [9]. Several scientific papers published in the last few years demonstrated that chemical substances do not necessarily exhibit oncogenic properties taken individually, but they may reveal dangerous effects in combination with other compounds owing to additive and synergistic effects, even at low doses [10]
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