Effects of phthalates on marine organisms: cytotoxicity and genotoxicity of mono-(2-ethylhexyl)-phthalate (MEHP) on European sea bass (Dicentrarchus labrax) embryonic cell line

Introduction. Mono-(2-ethylhexyl) phthalate (MEHP) represents a toxicological risk for marine organisms due to its widespread presence in aquatic environments. Methods. MEHP effects on cell viability, cell death and genotoxicity were investigated on the DLEC cell line, derived from early embryos of the European sea bass Dicentrarchus labrax L.Results. A dose-dependent cytotoxic effect, with no induction of necrotic process, except at its highest concentration, was observed. Moreover, chromosomal instability was detected, both in binucleated and mononucleated cells, coupled with a minor inhibition of cell proliferation, whereas genomic instability was not revealed. To our knowledge, the overall results suggest the first evidence of a possible aneugenic effect of this compound in the DLEC cell line, that is the induction of chromosomal loss events without the induction of primary DNA damage. Conclusions. MEHP should be considered more harmful than its parent compound DEHP, because it induces genomic instability in the DLEC cell line without triggering cell death

Bivalent nickel exposure induced mitotic toxicity in onion root tips

Nickel (Ni) is utilized across multiple industries, resulting in significant environmental contamination and exhibiting various genotoxic effects on plants and animals due to its release into the external environment. This study evaluates the cytotoxic effects of different doses of nickel on onion (Allium cepa L.) root tips. To evaluate the sensitivity of Nickel, bulbs of onion were treated at 10, 25, 50 and 100 ppm along with a control (0 ppm) using NiCl2 salt as the source of Nickel. At elevated concentrations of nickel (100 ppm) in a hydroponic study, the onion roots exhibited browning and translucency, accompanied by a retardation of growth. Various chromosomal anomalies, including chromosomal breaks, laggards, vagrant chromosomes, bridges, distorted chromosomes, sticky chromosomes, c-mitosis etc. were observed following a 24 hr exposure to toxic doses of nickel. Both types of chromosomal abnormalities, namely spindle fibre abnormality (SFA) and chromosomal abnormality (CA), were observed under Ni treatment. The evaluation of cell death in the treated roots was done using the Evans blue dye test. Uptake of Evans blue by the root cells demonstrated the cell death parameter, which served as an indicator of cytotoxicity

Phytotoxicity, cytotoxicity and genotoxicity evaluation of organic and inorganic pollutants rich tannery wastewater from a Common Effluent Treatment Plant (CETP) in Unnao district, India using Vigna radiata and Allium cepa

The leather industry is a major source of environmental pollution in India. The wastewater generated by leather industries contains very high pollution parameters due to the presence of a complex mixture of organic and inorganic pollutants even after the treatment at a Common Effluent Treatment Plant (CETP) and disturbs the ecological flora and fauna. The nature, characteristics and toxicity of CETP treated wastewater is yet to be fully elucidated. Thus, this study aims to characterize and evaluate the toxicity of CETP treated tannery wastewater collected from the Unnao district of Uttar Pradesh, India. In addition to measuring the physico-chemical parameters, the residual organic pollutants was identified by GC-MS analysis and phytotoxicity, cytotoxicity and genotoxicity of the treated wastewater was evaluated using Vigna radiata L. and Allium cepa L. Results showed that the treated wastewater contained very high pollution parameters (TDS 3850mg/L, BOD 680mg/L, COD-1300mg/L). GC-MS analysis revealed the presence of various types of residual organic pollutants including benzoic acid, 3-[4,-(T-butyl) Phenyl] furan-2-5-dione, benzeneacetamide, resorcinol, dibutyl phthalate, and benzene-1,2,4-triol. Further, toxicological studies showed the phytotoxic nature of the wastewater as it inhibited seed germination in V. radiata L. and root growth of A. cepa. Genotoxicity was evidenced in the root tip cell of A. cepa where chromosomal aberrations (stickiness, chromosome loss, C-mitosis, and vagrant chromosome) and nuclear abnormalities like micronucleated and binucleated cells were observed. Thus, results suggested that it is not safe to discharge these wastewater into the environment

Phytotoxicity, cytotoxicity and genotoxicity evaluation of organic and inorganic pollutants rich tannery wastewater from a Common Effluent Treatment Plant (CETP) in Unnao district, India using Vigna radiata and Allium cepa

The leather industry is a major source of environmental pollution in India. The wastewater generated by leather industries contains very high pollution parameters due to the presence of a complex mixture of organic and inorganic pollutants even after the treatment at a Common Effluent Treatment Plant (CETP) and disturbs the ecological flora and fauna. The nature, characteristics and toxicity of CETP treated wastewater is yet to be fully elucidated. Thus, this study aims to characterize and evaluate the toxicity of CETP treated tannery wastewater collected from the Unnao district of Uttar Pradesh, India. In addition to measuring the physico-chemical parameters, the residual organic pollutants was identified by GC-MS analysis and phytotoxicity, cytotoxicity and genotoxicity of the treated wastewater was evaluated using Vigna radiata L. and Allium cepa L. Results showed that the treated wastewater contained very high pollution parameters (TDS 3850mg/L, BOD 680mg/L, COD-1300mg/L). GC-MS analysis revealed the presence of various types of residual organic pollutants including benzoic acid, 3-[4,-(T-butyl) Phenyl] furan-2-5-dione, benzeneacetamide, resorcinol, dibutyl phthalate, and benzene-1,2,4-triol. Further, toxicological studies showed the phytotoxic nature of the wastewater as it inhibited seed germination in V. radiata L. and root growth of A. cepa. Genotoxicity was evidenced in the root tip cell of A. cepa where chromosomal aberrations (stickiness, chromosome loss, C-mitosis, and vagrant chromosome) and nuclear abnormalities like micronucleated and binucleated cells were observed. Thus, results suggested that it is not safe to discharge these wastewater into the environment

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Causes of genome instability: the effect of low dose chemical exposures in modern society.

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis

Causes of genome instability: the effect of low dose chemical exposures in modern society

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://carcin.oxfordjournals.org/. The publisher and the author(s) have made this article open access

Assessing the Carcinogenic Potential of Low-Dose Exposures to Chemical Mixtures in the Environment: The Challenge Ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety \u27Mode of Action\u27 framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology