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Although asbestos is carcinogenic to humans, the mechanism(s) by which it induces cancer is unknown. Using tumor cell lines generated previously by asbestos treatment of immortalized human bronchial epithelial (BEP2D) cells, we examined alterations in p16 and p21Cip1 genes together with their protein levels. Results were compared with untreated BEP2D cells, normal human bronchial epithelial cells (NHBE), as well as non-tumorigenic fusion cell lines generated by fusing tumor cells with BEP2D cells. No deletion in the p16 gene was found in any of the tumor cell lines examined. Although p16 protein was expressed at a similar level in tumor and BEP2D cells, there was a fourfold decrease in its expression among NHBE cells. In contrast, both the protein and mRNA expression levels of p21Cip1 were decreased by about threefold in tumor cell lines when compared with either BEP2D or NHBE cells, which had a similar expression level. Expression of p21Cip1 mRNA was restored to the control level in all the fusion cell lines examined. The results suggested that down regulation of p21Cip1 expression is linked to the tumorigenic conversion of BEP2D cells by asbestos. Oncogene (2001) 20, 7301–7306. [ABSTRACT FROM AUTHOR]

The cellular and molecular mechanisms of radiation-induced lung cancer are not known. In the present study, alterations of p53 in tumorigenic human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells induced by a single low dose of either α-particles or 1 GeV/nucleon 56Fe were analyzed by PCR–single-stranded conformation polymorphism (SSCP) coupled with sequencing analysis and immunoprecipitation assay. A total of nine primary and four secondary tumor cell lines, three of which were metastatic, together with the parental BEP2D and primary human bronchial epithelial (NHBE) cells were studied. The immunoprecipitation assay showed overexpression of mutant p53 proteins in all the tumor lines but not in NHBE and BEP2D cells. PCR–SSCP and sequencing analysis found band shifts and gene mutations in all four of the secondary tumors. A G→T transversion in codon 139 in exon 5 that replaced Lys with Asn was detected in two tumor lines. One mutation each, involving a G→T transversion in codon 215 in exon 6 (Ser→lle) and a G→A transition in codon 373 in exon 8 (Arg→His), was identified in the remaining two secondary tumors. These results suggest that p53 alterations correlate with tumorigenesis in the BEP2D cell model and that mutations in the p53 gene may be indicative of metastatic potential. [ABSTRACT FROM PUBLISHER]