Amelia K. Charles

Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

The alkyl esters of p‐hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF‐7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no‐observed‐effect concentrations (NOEC), lowest‐observed‐effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF‐7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF‐7 cells could be increased by combining all five parabens at concentrations down to the 50th percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF‐7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF‐7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright

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 genomes 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.

Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitro.

Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess oestrogenic activity in assays using the oestrogen‐responsive MCF7 human breast cancer cell line. At 3 000 000‐fold molar excess, they were able to partially displace [3H]oestradiol from recombinant human oestrogen receptors ERα and ERβ, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 × 10−5 to 5 × 10−4 m, they were able to increase the expression of a stably integrated oestrogen‐responsive reporter gene (ERE‐CAT) and of the endogenous oestrogen‐responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10−8 m 17β‐oestradiol. They increased the proliferation of oestrogen‐dependent MCF7 cells over 7 days, which could be inhibited by the antioestrogen fulvestrant, suggesting an ER‐mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10−8 m 17β‐oestradiol, given a longer time period of 35 days the extent of proliferation with 10−4 m benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10−8 m 17β‐oestradiol over 14 days. This demonstrates that benzyl salicylate, benzyl benzoate and butylphenylmethylpropional are further chemical components of cosmetic products which give oestrogenic responses in a human breast cancer cell line in culture. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues. Copyright