Correction to: Mode of action-based risk assessment of genotoxic carcinogens.

The author would like to thank N. Bakhiya, S. Hessel-Pras, B.

Mode of action-based risk assessment of genotoxic carcinogens.

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group.

Human relevance of follicular thyroid tumors in rodents caused by non-genotoxic substances.

Chronic stimulation of the thyroid gland of rodents by TSH leads to thyroid follicular hyperplasia and subsequently to thyroid follicular adenomas and carcinomas. However, the interpretations of rodent thyroid tumors are contradictory. The U.

[Metals and their compounds as contaminants in food : Arsenic, cadmium, lead and aluminum].

Metals and their compounds are ubiquitously distributed in the environment, thus reaching plant and animal derived food. While actual exposure levels in Europe do not give rise to concern for acute toxicity, chronic toxicity of some metals and metalloids cannot be completely ruled out. Thus, in the case of inorganic arsenic, an elevated risk of carcinogenicity in different organs cannot be excluded even under actual dietary exposure conditions.

Impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status.

The tumor suppressor protein p53, often called the guardian of the genome, is involved in important cellular processes, such as cell cycle control, apoptosis and DNA repair. With respect to BER, p53 might physically interact with and affect the transcription of different BER proteins such as hOGG1, APE1 or Polβ. In studies in HCT116 p53(-/-) cells previously published, activity and mRNA expression of hOGG1 were found to be significantly decreased, while down-regulation of APE1 mRNA and protein levels in response to genotoxic stress were only described in HCT116 p53(+/+) cells, but not in the isogenic p53 knockout cell line.

Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.

Human colon carcinoma cells (HCT116) differing in p53 status were exposed to benzo(a)pyrene (BaP) or anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) and their gene expression responses compared by complementary DNA microarray technology. Exposure of cells to BPDE for up to 24 h resulted in gene expression profiles more distinguishable by duration of exposure than by p53 status, although a subset of genes were identified that had significantly different expression in p53 wild-type (WT) cells relative to p53-null cells. Apoptotic signalling genes were up-regulated in p53-WT cells but not in p53-null cells and, consistent with this, reduced viability and caspase activity were also p53 dependent.

Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP-ribosyl)ation and PARP-1 activity.

Copper is an essential trace element involved, among other functions, in enzymatic antioxidative defense systems. However, nonprotein bound copper ions have been shown to generate reactive oxygen species. To gain insight into the discrepancy between the protective properties of copper on the one hand and its toxicity on the other hand, we examined the genotoxic effects of CuSO(4) in cultured human cells.