Humic acid induced genotoxicity in human peripheral blood lymphocytes using comet and sister chromatid exchange assay

Hseu, You Cheng; Chen, Ssu Ching; Chen, Ya Lai; Chen, Jing Yi; Lee, Mei Ling; Lu, Fung Jou; Wu, Fang; Lai, Jin‐Shin; Yang, Hsin Ling

doi:10.1016/j.jhazmat.2007.09.024

Cited by 28 publications

(19 citation statements)

References 40 publications

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“…Several studies have indicated that HA could induce oxidative injury (Jezierski et al 2000) mediated by superoxide anion production (Liang et al 1999) and apoptosis induction (Hseu et al 2000;Hseu et al 2002a, b;Yang et al 2004;Hseu et al 2008). Measurement of antioxidant properties of the selected natural HAs in both media showed that HAs displayed low antioxidant properties against superoxide radical, reaching maximally 20% of inhibition irrespective of the solvent used and the time of illumination (see Fig.…”

Section: Discussionmentioning

confidence: 89%

“…On the other hand, HAs have been suggested to be an etiological factor of cancer, with HAs induced oxidative damage as a potential causative mechanism of carcinogenesis (Hseu et al 2008). HAs are the most widespread natural polymers derived from biological, chemical and microbial decomposition of organic matter.…”

Section: Discussionmentioning

confidence: 99%

“…It was observed that interaction between HAs and endothelial cells may increase directly their Ca 2+ permeability, increase NO/peroxynitrite production and could lead to apoptotic cell death (Hseu et al 2002a, b). Via oxidative generation and reduction in the activities of antioxidant enzymes in human erythrocytes, HAs induced echinocyte transformation (Hseu et al 2000) and oxidative DNA damage in human peripheral blood lymphocytes (Hseu et al 2008). HAs stimulate rat liver mitochondria respiration (Visser 1987).…”

Section: Introductionmentioning

confidence: 99%

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Effects of humic acids in vitro

Vašková

Veliká

Pilátová

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

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Humic acids are known for their overall positive health and productivity effects in animal feeding trials and, controversially, as an aetiological factor of cancer. We tried to assess the in vitro effect of humic acids from a selected source in Slovakia when used at recommended prophylactic dosage. We investigated antioxidant properties, enzymatic and non-enzymatic antioxidant defence system in liver mitochondria and cultured cancer cell lines in vitro. We observed a significant decrease in superoxide dismutase activity after humic acids treatment irrespective of dissolving in dimethyl sulphoxide or direct addition to mitochondria suspension in a respiration medium. Activities of other antioxidant enzymes measured, such as glutathione peroxidase and glutathione reductase, showed no significant differences from the control as well as the reduced glutathione content. Percentage of inhibition by humic acids of superoxide radical indicated lower efficacy compared with that of hydroxyl radical. Survival of six different cancer cells lines indicated that only the acute T lymphoblastic leukaemia cell line was sensitive to the tested humic acids. Despite relatively low solubility in aqueous solutions, humic acids from the selected source participated in redox regulation. By recapturing the radicals, humic acids reloaded the antioxidant defensive mechanism. Results from in vitro study conducted with humic acids from the natural source showed potential of these substances as promising immunity enhancing agents.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of humic acids in vitro

Vašková

Veliká

Pilátová

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

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“…Sister chromatid exchanges (SCE) assay. Various cytomolecular protocols have been used to perform the sister chromatid exchanges (SCE) assay (Djelic et al, 2006;Kaya and Topaktas, 2007;Bakkali et al, 2008;Hseu et al, 2008). This method relies on the differential staining of sister chromatids during replication to visualize reciprocal genetic exchanges between them.…”

Section: In Vitro Methods For Genotoxicity Assessmentmentioning

confidence: 99%

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

Ouédraogo

Baudoux

Stévigny

et al. 2012

Journal of Ethnopharmacology

124

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“…HA and fulvic acids extracted from podzol stimulate respiration in rat liver mitochondria resulting in the generation of intracellular reactive oxygen species (ROS) (Visser, 1987). Moreover, HA can induce oxidative DNA damage and genotoxicity in human peripheral blood lymphocytes (Hseu et al, 2008). Therefore, we conclude that both oxidative stress and/or Ca 21 are mediators of cell toxicity caused by HA, however, HA toxicity has not been well demonstrated either in vitro or in vivo.…”

Section: Introductionmentioning

confidence: 92%

Humic acid induces G1 phase arrest and apoptosis in cultured vascular smooth muscle cells

Hseu

Lin

Chen

et al. 2008

Environmental Toxicology

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Humic acid (HA) in well water used by the inhabitants for drinking is one of the possible etiological factors for Blackfoot disease (BFD). In this study, the ability of HA to inhibit cell cycle progression and induce apoptosis in cultured smooth muscle cells (SMCs; A7r5) was investigated. Treatment of the SMCs at various HA concentrations (25-200 microg/mL) resulted in sequences of events marked by apoptosis, as shown by loss of cell viability, morphology change, and internucleosomal DNA fragmentation. HA-induced apoptotic cell death that is associated with loss of mitochondrial membrane potential (Delta Psi m), cytochrome c translocation, caspase-3, -8, and -9 activation, poly ADP-ribose polymerase (PARP) degradation, dysregulation of Bcl-2 and Bax, and upregulation of p53 and phospholyrated p53 (p-p53) in SMCs. Flow cytometry analysis demonstrated that HA blocked cell cycle progress in the G1 phase in SMCs. This blockade of cell cycle was associated with reduced amounts of cyclin D1, CDK4, cyclin E, CDK2, and hyperphosphorylated retinoblastoma protein (pRb) in a time-dependent manner. Apparent DNA strand breaks (DNA damage) were also detected in a dose-dependent manner using Single-cell gel electrophoresis assay (comet assay). Furthermore, HA induced dose-dependent elevation of reactive oxygen species (ROS) level in SMCs, and antioxidant vitamin C and Trolox effectively suppressed HA-induced DNA damage and dysregulation of Bcl-2/Bax. Our findings suggest that HA-induced DNA damage, cell cycle arrest, and apoptosis in SMCs may be an underlying mechanisms for the atherosclerosis and thrombosis observed in the BFD endemic region.

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Humic acid induced genotoxicity in human peripheral blood lymphocytes using comet and sister chromatid exchange assay

Cited by 28 publications

References 40 publications

Effects of humic acids in vitro

Effects of humic acids in vitro

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

Humic acid induces G1 phase arrest and apoptosis in cultured vascular smooth muscle cells

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