New models for assessing carcinogenesis: an ongoing process.
Traditionally, the use of rodent models in assessing the carcinogenic potential of chemicals has been expensive and lengthy, and the relevance of the carcinogenic effect to humans is often not fully understood. Today, however, with the rapid advances in molecular biology, genetically altered mice containing genes relevant to humans (e.g. oncogenes, tumor suppressor genes) and reporter genes (e.g. lacI) provide powerful tools for examining specific chemical-gene interactions thereby allowing a better understanding of the mechanisms of carcinogenesis in a shorter period of time. This paper will cover an overview of ongoing validation efforts, followed by examples of studies using several genetically engineered models including the p53def mouse model and the Big Blue transgenic mouse model. Specifically, examples where transgenic models were integrated into the testing program based on specific hypotheses dealing with genetic alterations in cancer genes and reporter genes will be discussed. The examples will highlight possible ways genetically altered mice may be integrated into a comprehensive research and testing strategy and thereby provide an improved estimation of human health risks.
Sills
R C
RC
Laboratory of Experimental Pathology, MD: B3-08, National Institute Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. sills@niehs.nih.gov
French
J E
JE
Cunningham
M L
ML
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001554:Benzene / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000633:toxicity; D002070:Butadienes / Q000633:toxicity; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D029968:Escherichia coli Proteins; D016158:Genes, p53 / Q000502:physiology*; D056968:Lac Repressors; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010076:Oxazepam / Q000633:toxicity; D020113:Phenolphthalein / Q000633:toxicity; D012097:Repressor Proteins / Q000235:genetics; D014520:Urethane / Q000633:toxicity
D001426:Bacterial Proteins; D002070:Butadienes; D002273:Carcinogens; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D012097:Repressor Proteins; D001564:Benzo(a)pyrene; D014520:Urethane; D010076:Oxazepam; D020113:Phenolphthalein; D001554:Benzene; C031763:1,3-butadiene