Inducible processes in human cells by low doses of genotoxic physical and chemical factors

Abstract

We are continuously exposed to low levels of genotoxic agents from our indoor and outdoor environment. Human cells have different responses to continuous DNA damage, depending on the DNA repair capacity and related factors. Exposure to very low levels of alkylating agents for one or two cell cycles renders the cells more resistant due to the induction of DNA methyltransferase. Exposure of NOx can lead to formation of N‐nitroso compounds in the human body which may act in a similar way. Nucleotide excision repair may also be inducible by factors which alter chromatin to allow recognition of the damage and their subsequent repair. The heterogeneous nature of repair in the genome can be considered, within the chromatin, at several different organisational levels. Our studies on inhabitants of an area of high natural radioactivity in Austria will be discussed with respect to increased DNA excision repair and increased poly‐(ADP‐ribose)‐polymerase activity. Establishing acceptably low exposure limits to carcinogens in our environment is a major problem faced by regulatory agencies today. It is recommended that the low dose linear extrapolation model, (which is often used in assessing low level environmental risk for healthy people), should be adjusted in recognition of data obtained on DNA repair and other inducible processes