Oxidative DNA damage contributes to the toxic activity of propylparaben in mammalian cells

Pérez-Martı́n, José; Peropadre, Ana; Herrero, Óscar; Freire, Paloma Fernández; Labrador, V.; Hazen, M.J.

doi:10.1016/j.mrgentox.2010.07.012

Cited by 61 publications

(24 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, PP showed the lowest IC 50 value, which could suggests that it is more cytotoxic than MP (this could probably be explained by its higher lipophilicity). Martín et al. have recently (2010) reported that PP causes changes in cell proliferation values rather than in cell viability and induces DNA double‐strand breaks.…”

Section: Discussionmentioning

confidence: 99%

“…Fragrances and preservatives used in cosmetics are among the most common allergens in contact dermatitis [3][4][5][6]; however, recent reports from Turkey indicated a relatively low sensitization rate [7].Concentration of the same preservative in similar products varies greatly, and excessive preservation of cosmetics potentially can lead to increased incidences of contact allergy, depending on the allergic potential of the preservative or interaction with other ingredients. Some preservatives such as parabens are reported to cause other adverse effects, environmental pollution, carcinogenicity and hormonal disturbances or changes, but these effects vary with the preservative substance [8,9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro induction of apoptosis, necrosis and genotoxicity by cosmetic preservatives: application of flow cytometry as a complementary analysis by NRU

Carvalho¹,

Menezes²,

Letenski³

et al. 2011

Intern J of Cosmetic Sci

View full text Add to dashboard Cite

Preservatives are used in cosmetics to prevent microbial contamination; however, some preservatives are not free of allergenic and cytotoxic potential. Allergenicity and cytotoxicity potential values are major aspects of preservative safety, which determine limitations and maximum concentration dose in a cosmetic product. The purpose of this study was to investigate and compare the in vitro apoptosis, necrosis and genotoxicity-inducing potential of five different types of preservatives: Phenoxyethanol (PE), Propylparaben (PP), Methylparaben (MP), Benzyl Alcohol (BA) and Ethylhexyl Glycerine (EG). In vitro experiments were carried out on human dermal fibroblasts by a quantitative flow cytometry method, using specific cell markers (Annexin V, Propidium Iodide and H2AX). We compared the resulting cell viability by means of neutral red uptake (NRU) and established the IC(50) . Our results showed that PE, PP, MP and BA have similar cytotoxic mechanisms (high apoptosis and necrosis levels only at the test concentration of 1%), whereas EG showed only an apoptosis pathway. For genotoxicity, both parabens yielded the highest values. Results obtained by flow cytometry for necrosis were comparable to those produced by NRU; however, NRU does not distinguish apoptosis from necrosis. We propose that flow cytometry is a more sophisticated methodology for understanding the cytotoxic mechanisms of cosmetic preservatives and can be used to complement the NRU.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro induction of apoptosis, necrosis and genotoxicity by cosmetic preservatives: application of flow cytometry as a complementary analysis by NRU

Carvalho¹,

Menezes²,

Letenski³

et al. 2011

Intern J of Cosmetic Sci

View full text Add to dashboard Cite

show abstract

“…In Chinese hamster ovary (CHO‐K1) cells, treatment with propylparaben or butylparaben for 1 h increased DNA fragmentation (DNA strand break) as measured using a comet assay, induced chromosome aberrations and increased sister‐chromatid exchanges (Tayama et al ., ). In the Vero cell line derived from green monkey kidney, exposure to propylparaben for 24 h caused cell cycle arrest at the G 0 /G 1 phase of the cell cycle rather than loss of cell viability and this was associated with induction of DNA double‐strand breaks and oxidative damage demonstrated using immunodetection techniques (Martin et al ., ). A correlative study of human urinary exposure to parabens and markers of male reproductive health in the USA showed a link between urinary level of butylparaben and sperm DNA damage (Meeker et al ., ).…”

Section: Enabling Characteristics: Genomic Instabilitymentioning

confidence: 97%

Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status

Darbre

Harvey

2014

J of Applied Toxicology

146

View full text Add to dashboard Cite

A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1, parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. In Hallmark 2, parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by growth inhibitors. In Hallmark 3, in the 10 nm-1 μm range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue.

show abstract

“…Although parabens have been subjected to classic toxicology testing and have been reported as negative in the classic Ames test for carcinogenicity (Andersen, ; Golden et al ., ; Soni et al ., ), there was one report of mammary fibroadenomas in rats treated longer term (up to 52 weeks) with methylparaben (Andersen, ) and several reports have associated paraben with DNA damage (Martin et al ., ; Meeker et al ., ; Okamoto et al ., ; Tayama et al ., ). Their ability to induce a transformed phenotype in an in vitro assay which is predictive of ability to induce tumours in vivo (Shin et al ., ) and to do so in human breast epithelial cells deserves further investigation into a potential link between parabens and breast carcinogenesis which has not previously been recognized.…”

Section: Discussionmentioning

confidence: 98%

Parabens enable suspension growth of MCF‐10A immortalized, non‐transformed human breast epithelial cells

Khanna

Darbre

2012

J of Applied Toxicology

View full text Add to dashboard Cite

Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10(-6) M methylparaben, 10(-7) M n-propylparaben and 10(-7) M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

show abstract

Oxidative DNA damage contributes to the toxic activity of propylparaben in mammalian cells

Cited by 61 publications

References 45 publications

In vitro induction of apoptosis, necrosis and genotoxicity by cosmetic preservatives: application of flow cytometry as a complementary analysis by NRU

In vitro induction of apoptosis, necrosis and genotoxicity by cosmetic preservatives: application of flow cytometry as a complementary analysis by NRU

Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status

Parabens enable suspension growth of MCF‐10A immortalized, non‐transformed human breast epithelial cells

Contact Info

Product

Resources

About