Cytotoxic effects of environmentally relevant chlorophenols on L929 cells and their mechanisms

Abstract

The chlorophenol chemicals (CPs) are a major class of widely distributed and frequently occurring persistent environmental pollutants. Pentachlorophenol (PCP) has been proposed to be procarcinogen in rodents and in possibly human beings. Human beings also easily expose to other chlorophenol chemicals, including 4-chlorophenol (CP), 2,4-dichlorophenol (DCP), 2,3,4-trichlorophenol (TCP), prompting this investigation of their comparative cytotoxic effects and cell death mechanisms, assayed in fibroblast L929 cells. The effective concentration for half-maximal response (EC50 values at 24 h for CP, DCP, TCP, and PCP are 2.18, 0.83, 0.46, and 0.11 mmol/L respectively and the EC50 values at 48 h are 1.18, 0.13, 0.08, and 0.06 mmol/L respectively by using 3-(4,5-dimethylthiazd-2-yl)-2,5-diphenyltentrazolium bromide (MTT) reduction assay. A clear structure-activity relationship was observed between toxicity of CPs and their octanol-water partition coefficients. The further studies indicate that CP, DCP, and TCP induce apoptosis in L929 cells in a concentration or time-dependent manner, but PCP mediates cell death more characteristic of necrosis than apoptosis. These results not only demonstrate that L929 cell growth inhibition bioassay may be useful to provide the comparative evaluation of toxicity of CPs in vitro, but also implicate that CP, DCP, TCP, in comparison with PCP, can induce L929 cell death by apoptosis, resulting in lower procarcinogensis, which may help to elucidate the molecular basis for the adverse health effects associated with CPs exposure.

Prediction of Environmental Properties for Chlorophenols with Posetic Quantitative Super-Structure/Property Relationships (QSSPR)

“…Chlorophenols are widely used as bactericides, insecticides, herbicides, fungicides and wood preservatives [13][14][15][16][17][18][19][20][21], which makes them frequent environmental pollutants, either from direct use or accidental spillage. Exposure to chlorophenols can result in irritations of the respiratory tract and of the eyes.…”

“…The United States Environmental Protection Agency (EPA) has classified chlorophenols as priority pollutants owing to their environmental toxicity. Due to their wide use in industry and the household (as bactericides, insecticides, herbicides, fungicides, and wood preservatives) [13][14][15][16][17][18][19][20][21], chlorophenols are easily released in the environment, either from direct use or accidental spillage. As a consequence, they cause severe environmental problems, being frequently detected in surface water, wastewater, soil, and sediments [17,34,35].…”

“…Phenol and its derivatives are common environmental contaminants [13][14][15][16][17][18], and most of them are known or suspected to be human carcinogens. Besides the fact that phenols give an unpleasant taste and odor to drinking water, they are powerful toxics for various biological processes.…”

Detection and mechanistic investigation of halogenated benzoquinone induced DNA damage by photoelectrochemical DNA sensor

“…Reactivity of these chlorophenols toward dG and calf thymus DNA following activation by horseradish peroxidase/H 2 O 2 has been established [16][17][18], and the formation of 2,5-DCBQ-DNA and 2,6-DCBQ-DNA adducts was observed [19].…”

Short-Term Bioassay of Chlorophenol Compounds Using Euglena gracilis

“…Due to their high toxicity, chemical stability, and bioaccumulation in living organisms, they are listed as the most toxic environmental pollutants by US EPA [6]. 2,4-Dichlorophenol (2,4-DCP) is a cytotoxic compound towards marine and fresh water algae as well as animal cells [7][8][9][10]. Pentachlorophenol (PCP) causes liver, adrenal gland, and nasal tumours in laboratory tested animals; in addition it causes liver and nervous system disorder for humans [11].…”