Chloracne is an acne-like eruption of blackheads, cysts, and pustules associated with over-exposure to certain halogenated aromatic compounds, such as chlorinated dioxins and dibenzofurans.
The team of researchers headed by ETH-Zurich professor Sabine Werner and a senior researcher of her team, Dr Matthias Schäfer stumbled across a link between chloracne and a molecular switch, which causes a comparable skin phenotype in mice after longer and increased activation.
The molecular switch is Nrf2, an antioxidant response pathway linked to stress, and the team had originally been trying to understand what takes place in the event of an increased activation of it in the skin, before discovering it as a major player in the development of chloracne.
Skin care interest
The latest discovery means Nrf2 is an interesting candidate for use in skin care creams and for cancer prevention, as, until now, prolonged activation in the skin had not been characterized.
Nrf2 is a transcription factor that activates certain genes that protect cells and help them to survive under stress conditions.
A few years ago, a research team from ETH-Zurich discovered that a moderate activation of Nrf2 protects the skin against UV damage, as the molecule activates several genes designed to protect skin cells from aggressive free radicals and prevents damage of the genetic material.
In this latest study, published in EMBO Molecular Medicine, the scientists used an animal model in which the skin cells of genetically modified mice permanently activated Nrf2.
As a result, the animals developed skin changes. In mice with Nrf2 activation, the sebaceous glands became enlarged and secreted an excessive amount of sebum.
The hair follicles were also thickened and callused, which ultimately led to their widening, hair loss and eventually the development of cysts.
Consequently, in a second step the scientists tested tissue samples from MADISH (a form of dioxin poisoning which leads to chloracne) patients and discovered that Nrf2 was evidently activated in their skin, causing a strong expression of the same target proteins as in the mouse model.
Therefore, it is very likely that the processes that triggers such abnormal skin changes in mice also take place very similarly in humans.
"We only spotted the link between chloracne and the mouse model in the course of our project -- purely by chance," says Werner.