Discovery in the 1970s

Decades of research around the subject of the dioxin receptor (aryl hydrocarbon receptor) not only permits us an insight into the relationships between exposures to hazardous substances and the occurrence of most severe diseases, but it also explains the cross-generational damage in our genome. As the beginnings of this research are largely unknown to most people, we are going to take a closer look at this issue, not least to appreciate and acknowledge the work of the pioneers in this field.

We do not know whether the medical researchers Nebert and Poland were aware of the dimension of their research activities in the early 1970s. Irrespective of this matter, their work provides the basis for an answer to the questions about the cause of most civilization diseases.

Simply put, Nebert and Poland were concerned with the investigation of the dioxin pollutant metabolism in genetically modified mouse strains (C57BL/6 and DBA/2N) at the beginning of their research work. In doing so they found out that the mouse strains reacted in extremely different ways to the dioxin exposure.

While the members of one mouse family died - as expected - as a result of dioxin poisoning, a much lower toxic effect was observed in the mouse variant that had been genetically modified by means of inbreeding.

A second group of mice that had undergone further genetic modification still by means of inbreeding finally demonstrated a complete dioxin resistance, i.e., the mice were absolutely immune to the most toxic of all toxins, the Seveso dioxin TCDD.

Nebert and his colleagues discovered that the mouse strains differed from each other by an unequally strong production of a certain enzyme (aryl hydrocarbon hydroxylase). The mouse strain that has almost no problem with the dioxin intake is neither capable of distributing this enzyme later referred to as “cytochrome P450 1A1“, nor of generating it.

Besides other researchers, it was chiefly Poland (and Knutson) who identified a certain protein on the cell surface as contact site (receptor) for dioxin and similar hazardous substances in addition to the modified enzyme distribution. And it was Poland, too, who named this receptor “aryl hydrocarbon receptor” for the first time in 1982. (Note: substances that are capable of binding to this receptor are referred to as ligands).

After the works of Nerbert and Poland on the Ah receptor had been published in the early 1970s, the number of the researchers in this field increased substantially around the world.