p27(Kip1) (Cdkn1b)-deficient mice are susceptible to chemical carcinogenesis and may be a useful model for carcinogen screening.
The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchanged for the last 25 years is a testament to the power of this approach to identify carcinogens and thus to minimize human exposure. However, there has long been controversy over the specificity and relevance of the rodent bioassay as well as its high cost in terms of time, expense, and numbers of mice. Much discussion has been generated in recent years over how to improve the 2-year rodent bioassay for more accurate and faster detection of potential human carcinogens. Here, we argue that the use of p27(Kip1) (Cdkn1b) knockout mouse for carcinogen screening may solve several shortcomings inherent in the conventional bioassay while preserving its best quality, that is, protecting public health by providing reliable in vivo information on the potential of chemicals to cause cancer.
Payne
Shannon R
SR
Fred Hutchinson Cancer Research Center C1-015, PO Box 19024, 1100 Fairview Ave N., Seattle, Washington 90109-1024, USA.
Kemp
Christopher J
CJ
D000818:Animals; D001681:Biological Assay / Q000379:methods; D015197:Carcinogenicity Tests / Q000379:methods; D002274:Carcinogens, Environmental / Q000633:toxicity*; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000172:deficiency*
D002274:Carcinogens, Environmental; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27