p53 gene mutations in neoplastic transformation of C3H 10T1/2 and severe combined immunodeficiency fibroblasts

Thr relevance of p53 mutations to the neoplastic malignant transformation o f rodent fibroblasts by genotoxic physical and chemical agents is not clear . In the present study, we investigated p53 mutations (in exons 5-8) in non -transformed and neoplastically transformed C3H 10T1/2 and severe combined immunodeficiency (SCID) cells. No p53 mutations were detected in 15 neoplas tically transformed (two spontaneous, one 3-methylcholanthrene-induced, sev en gamma-ray-induced and five 'hot particle'-induced) and two non-transform ed 10T1/2 cells, Wild-type p53 gene was also detected in all non-transforme d (immortalized) SCID cell lines analyzed (four lines) whereas all three ne oplastically transformed (two spontaneous, one gamma-ray-induced) cell line s displayed missense mutations in the p53 gene. These mutations were all tr ansitions: A > G in codon 123, G > A in codon 15, and C > T in codon 238, W e conclude that mutation in the p53 gene appears to be an infrequent event in 10T1/2 cells regardless of the transforming agent, but a frequent event in the neoplastic transformation of immortalized SCID cells. Non-transforme d SCID cells are deficient in repair of DNA double-strand breaks, and neopl astically transformed cells are assumed to be deficient as well. (C) 1999 E lsevier Science B.V, All rights reserved.