Zur frage einer unwirksamen dosis genotoxischer agenzien

Translated title of the contribution: The question of an ineffective dose of genotoxic agents

H. Greim, R. A. Albertini

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Although cellular integrity is constantly threatened by DNA damage arising from numerous intrinsic and environmental sources, cellular homeostasis remains unaffected at least at low dose exposures. To ensure protection of the genome, mammalian cells have developed different mechanisms. Mild DNA damage is normally eliminated by DNA repair; more severe or irreparable DNA damage triggers the induction of cell death programmes such as apoptosis or necrosis to avoid multiplication of damaged DNA by cell division. These mechanisms are quite effective. Whereas endogenous, mostly oxidative metabolism creates about 10,000 DNA lesions per cell per day, the steady State level of DNA adducts of a normal cell is about 500 altered bases. Although these defence mechanisms are increasingly being understood, the critical and rate limiting parameters and their dose response to the insulting agent are poorly evaluated. By describing the different mechanisms and their regulation, we intend to stress the need for such Information to further evaluate the plausibility of a dose-dependent and threshold mechanism of genotoxic carcinogens. Besides its scientific value, a better understanding of cellular defence and the onset of such counterbalancing reactions is of regulatory importance, because a scientifically defendable threshold concept for genotoxic carcinogens will allow identification of NOAELs and the derivation of health-based exposure limits.

Translated title of the contributionThe question of an ineffective dose of genotoxic agents
Original languageGerman
Pages (from-to)896-903
Number of pages8
JournalArbeitsmedizin Sozialmedizin Umweltmedizin
Volume50
Issue number12
StatePublished - Dec 2015
Externally publishedYes

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