Deregulation of cyclin E expression and/or high levels have been reported in a variety of tumors and have been used as indicators of poor prognosis. Although the role that cyclin E plays in tumorigenesis remains unclear, there is evidence that it confers genomic instability when deregulated in cultured cells. Here we show that deregulated expression of a hyperstable allele of cyclin E in mice heterozygous for p53 synergistically increases mammary tumorigenesis more than that in mice carrying either of these markers individually. Most tumors and tumor-derived cell lines demonstrated loss of p53 heterozygosity. Furthermore, this tumor susceptibility is related to the number of times the transgene is induced indicating that it is directly attributable to the expression of the cyclin E transgene. An indirect assay indicates that loss of p53 function is an early event occurring in the mammary epithelia of midlactation mammary glands in which cyclin E is deregulated long before evidence of malignancy. These data support the hypothesis that deregulated expression of cyclin E stimulates p53 loss of heterozygosity by promoting genomic instability and provides specific evidence for this in vivo. Cyclin E deregulation and p53 loss are characteristics often observed in human breast carcinoma.

Electrical Impedance Spectroscopy has been developed as a potential method for the diagnosis of carcinoma in epithelial tissues. An understanding of the influence of structural changes in the tissue on the properties measured using this technique is essential for interpreting measured data and optimisation of probe design. In contrast to other tissue types, carcinoma in Situ of the bladder gives rise to an increase in electrical impedance over the kHz-MHz frequency range in comparison to normal tissue. Finite element models of the • A Keshtkar,is now at: Medical Physics Department, Faculty of Medicine, Tabriz University of Medical Sciences,Tabriz-Iran urothelium and the underlying superficial lamina propria have been constructed and solved in order to ascertain the influence of structural changes associated with malignancy, oedema and inflammation on the measured electrical properties of the tissue. Sensitivity analysis of results from a composite tissue model suggests that the increase in lymphocyte density in the lamina propria associated with an inflammatory response to the infiltration of urine into the tissue may explain these unusual electrical properties.