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5970577 
Journal Article 
Abstract 
Toxicogenomic profiling of formaldehyde-dependent effects in vitro 
Ceder, R; Merne, M; Nilsson, JA; Staab, C; Höög, JO; Grafström, RC 
2012 
1 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
211 
Suppl. 
S195 
English 
WOS:000305173900636 
Toxicogenomics in vitro might serve to generate novel toxicity biomarkers and support the replacement of animals in toxicity testing. Toxicity of formaldehyde (FA), a human carcinogen, was studied in a cell culture model for cancer development, including normal (NOK), immortalized (SVpgC2a), and malignant (SqCC/Y1) cells. Repeated 1 h FA exposure of SVpgC2a caused cell transformation as indicated from the evolution of a new cell line following a crises period. The new line, termed SVpgC3a, exhibited altered morphology, soft agar growth, but was non-tumorigenic in athymic nude mice. Cytotoxicity and genotoxicity assessments indicated similar initial damage levels in all lines, whereas the longer-term consequences differed (toxicity assessments indicated a sensitivity order of NOK > SVpgC2a > SVpgC3a≈SqCC/Y1). FA induced cell death primarily by terminal differentiation in NOK whereas SVpgC2a, SVpgC3a and SqCC/Y1 died by other means e.g., apoptosis. Over a dose range, the highest level of genetic damage in SVpgC2a was observed at the concentration that induced transformation. Proteomics and transcriptomics profiling showed that cell transformation coupled with multiple changes in single genes, gene ontologies and molecular networks. Likewise, transcript profiling of the respective cell lines for up to 48 h following FA exposure indicated multiple genomic changes, some of which overlapped to results from cancer-inducing protocols in vivo. In conclusion, the sensitivity to FA toxicity might differ between stages in cancer development. Specific gene expression changes coupled to the respective phenotypes. The SVpgC3a cell line extended the current cancer model of normal, immortal and malignant cells. 
48th Congress of the European Societies of Toxicology (EUROTOX) 
Stockholm, Sweden 
June 17-20, 2012