Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice.

The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tissue-specific regulation of p53 transcriptional activity, we performed an extensive study looking at the expression of four well characterized p53-responsive genes, before and after gamma-irradiation in p53 wild-type (p53+/+) and p53-deficient (p53-/-) mice.

Tumour suppressor protein p53 released by nuclease digestion increases at the onset of rat liver regeneration.

Background/aims: Protein kinase CK2 (CK2) increases when cells are committed to proliferate, as in liver regeneration. This enzyme phosphorylates the tumour suppressor protein p53, whose expression controls the levels of many other cell cycle proteins. The aim of this study was to determine if CK2 was affected by p53.

Prolonged p53 protein accumulation in trichothiodystrophy fibroblasts dependent on unrepaired pyrimidine dimers on the transcribed strands of cellular genes.

Trichothiodistrophy (TTD), xeroderma pigmentosum (XP), and Cockayne's syndrome (CS) are three distinct human diseases with sensitivity to ultraviolet (UV) radiation affected by mutations in genes involved in nucleotide excision repair (NER). Among the many responses of human cells to UV irradiation, both nuclear accumulation of p53, a tumor suppressor protein, and alterations in cell-cycle checkpoints play crucial roles. The purpose of this study was to define the signals transmitted after UV-C-induced DNA damage, which activates p53 accumulation in TTD/XP-D fibroblasts, and compare this with XP-D cell lines that carry different mutations in the same gene, XPD.

Concomitant p53 gene mutation and increased radiosensitivity in rat lung embryo epithelial cells during neoplastic development.

A rat lung cell population had been treated with benzo(a)pyrene, and a set of different epithelial cell lines was derived from it. These cell lines carried either a wild-type or mutant p53 gene and represented grading states of neoplastic development. We demonstrate here that the cells lacking both wild-type p53 alleles display a significant decrease in survival after gamma-irradiation with doses of 2 to 12 Gy, compared with their counterparts carrying wild-type p53 alleles.

Directional selection associated with clonal expansion of p53 mutant cells during neoplastic development of carcinogen-treated rat embryo lung epithelial cells.

In this study, rat embryo lung organ cultures were exposed to benzo[a]pyrene (B[a]P). After carcinogen-treatment the cells were dissociated and an epithelial cell line (BP) was developed from the primary cell culture derived from the carcinogen-treated explants. Investigations were performed on the sequential changes occurring in the course of neoplastic progression of BP cells and in the tumor cells that arose in vivo from implanted BP cells.