A comet assay study reveals that aluminium induces DNA damage and inhibits the repair of radiation-induced lesions in human peripheral blood lymphocytes

Lankoff, Anna; Banasik, Anna; Duma, Anna; Ochniak, Edyta; Lisowska, Halina; Kuszewski, Tomasz; Góźdż, Stanisław; Wójcik, Andrzej

doi:10.1016/j.toxlet.2005.07.012

Cited by 119 publications

(67 citation statements)

References 38 publications

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“…Based on this observation, on the large array of effects by which aluminium has been reported to affect cellular physiology, including genotoxicity (Kawahara and Kato-Negishi, 2011;Banasik et al, 2005;Lankoff et al, 2006), on its wellestablished neurotoxic profile (Kawahara and Kato-Negishi, 2011;Krewski et al, 2007), and on its high concentration in antiperspirants, it has been hypothesized that aluminium might play a causal role in the carcinogenesis of the human mammary epithelium (Darbre, 2003(Darbre, , 2005. However, very little or no experimental data supporting this hypothesis exist.…”

Section: Discussionmentioning

confidence: 99%

“…In the latter cell type, this effect correlated with the induction of apoptosis (Banasik et al, 2005;Lankoff et al, 2006). Although the molecular basis of the genotoxic effect of aluminium has not been defined, it has been hypothesized to be mediated by direct interaction of aluminium with DNA, by the induction of oxidative DNA damage, by the release of lysosomal DNase, or by interference with normal microtubule function or with cellular DNA repair mechanisms (Banasik et al, 2005;Lankoff et al, 2006;Kawahara and Kato-Negishi, 2011). As discussed above, the effect of aluminium on human mammary epithelial cells reported in this study seems to be mediated in part by proliferation stress.…”

Section: Discussionmentioning

confidence: 99%

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Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

Sappino

Buser

Lesne

et al. 2012

J of Applied Toxicology

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Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl 3 ) concentrations of 10-300 mM, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl 3 also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl 3 display strong upregulation of the p53/p21Waf1 pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl 3 generates and selects for cells able to bypass p53/p21 Waf1 -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

Sappino

Buser

Lesne

et al. 2012

J of Applied Toxicology

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“…One consequence of Al treatment is increased DNA fragmentation (Lankoff et al, 2006;Achary et al, 2008;Rounds and Larsen, 2008;Yi et al, 2010), although it is unclear whether this DNA damage is relevant to Al-dependent root growth inhibition. To determine the extent of DNA fragmentation in alt2-1 roots after Al treatment, wild-type Col-0 and alt2-1 seedlings were grown for 7 d in the absence or presence of 1.50 mM AlCl 3 in a soaked gel environment (pH 4.2), after which root tips were harvested for isolation of nuclei for analysis of DNA integrity using the Comet assay under neutral conditions.…”

Section: Alt2 Functions As An Al-responsive Cell Cycle Checkpointmentioning

confidence: 99%

The Arabidopsis Cell Cycle Checkpoint Regulators TANMEI/ALT2 and ATR Mediate the Active Process of Aluminum-Dependent Root Growth Inhibition

et al. 2012

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Aluminum (Al) toxicity is a global issue that severely limits root growth in acidic soils. Isolation of suppressors of the Arabidopsis thaliana Al-hypersensitive mutant, als3-1, resulted in identification of a cell cycle checkpoint factor, ALUMINUM TOLERANT2 (ALT2), which monitors and responds to DNA damage. ALT2 is required for active stoppage of root growth after Al exposure, because alt2 loss-of-function mutants fail to halt root growth after Al exposure, do not accumulate CyclinB1;1 in the root tip, and fail to force differentiation of the quiescent center. Thus, alt2-1 mutants are highly tolerant of Al levels that are severely inhibitory to the wild type. The alt2-1 allele is a loss-of-function mutation in a protein containing a putative DDB1-binding WD40 motif, previously identified as TANMEI, which is required for assessment of DNA integrity, including monitoring of DNA crosslinks. alt2-1 and atr loss-of-function mutants, the latter of which affects the cell cycle checkpoint ATAXIA TELANGIECTASIA-MUTATED AND RAD3-RELATED, are severely sensitive to DNA crosslinking agents and have increased Al tolerance. These results suggest that Al likely acts as a DNA-damaging agent in vivo and that Al-dependent root growth inhibition, in part, arises from detection of and response to this damage by TANMEI/ALT2 and ATR, both of which actively halt cell cycle progression and force differentiation of the quiescent center.

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“…[7][8][9][10][11][12][13][14][15][16] Recently, Al was shown to induce DNA damage and endoreduplication and to have clastogenic effects in human lymphocytes incubation. [17][18][19] The Al-DNA adduct was identified in clinic samples. 20 Three Al-DNA complexes were proposed before two decades when ds-DNA was denatured at pH 5.0 -7.0 with the mole ratios of Al:DNA from 0 to 0.7 and at pH 6.5 -7.5, when the mole ratio was higher than 0.8, DNA precipitation was also observed.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical and Spectrometric Studies of Double-Strand Calf Thymus Gland DNA Denatured by Al(III) at Neutral pH

et al. 2009

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The interaction between double-strand calf thymus gland DNA (ds-DNA) and Al(III) was studied by using differential pulse voltammetry (DPV) at a hanging mercury drop electrode (HMDE), Raman spectrometry and circular dichroism (CD) spectra. It was shown that at neutral pH ds-DNA did not produce any cathodic peak at the HMDE in the potential window from -550 to -2000 mV vs. SCE. However, in the presence of Al(III), a cathodic peak was generated at about -1660 mV, which is ascribed to a reduction of adenine and cytosine residues of single denatured DNA (sd-DNA). It was concluded that ds-DNA was completely denatured to sd-DNA by Al(III) at a neutral pH. The apparent denaturing kinetic velocity constants of ds-DNA by Al(III) were derived from linear increases of the cathodic peak currents with time.3 ≥ 2 × 10 -26 , the precipitation of Al(OH)3 was observed and identified by the Raman spectrum, and inductively coupled plasma atomic emission spectrometry (ICP-AES). CD spectra showed that the B-type of structure conformations of ds-DNA and related sd-DNA did not change with the increment of Al(III) from 5.0 × 10 -7 to 1.0 10 -5 M, but the corresponding absorption strengths increased. The related physiological significances and possible applications of the observations were considered.

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A comet assay study reveals that aluminium induces DNA damage and inhibits the repair of radiation-induced lesions in human peripheral blood lymphocytes

Cited by 119 publications

References 38 publications

Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

The Arabidopsis Cell Cycle Checkpoint Regulators TANMEI/ALT2 and ATR Mediate the Active Process of Aluminum-Dependent Root Growth Inhibition

Electrochemical and Spectrometric Studies of Double-Strand Calf Thymus Gland DNA Denatured by Al(III) at Neutral pH

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