INDUCTION OF HYPERDIPLOIDY AND CHROMOSOME BREAKS IN LIM1215 CELLS EXPRESSING THE EXOGENOUS MUTANT P53

The effect of modifications of p53 expression on the incidence of nume rical and structural chromosome aberrations was studied. Infection of LIM1215 cells containing two alleles of the wild-type p53 gene (P53wt) with the recombinant viruses that expressed mutant cDNAs coding for h uman p53 (His273, Trp248, and His175) resulted in appearance of hyperd iploid cells in populations and an increased proportion of metaphases with chromosome breakage. Expression of the exogenous p53wt or vectors HSG/neo and pPS/neo, which did not contain the p53 cDNA, did not indu ce numerical or structural chromosome aberrations. Treatment of cells with caffeine decreased the p53wt content and increased the proportion of metaphases with chromosome breaks; however, it did not induce hype rdiploidy in the majority of cell lines. Only in the subline that expr essed the exogenous p53Trp248 did caffeine treatment increase the prop ortion of hyperdiploid variants, which was correlated with the hyperex pression of the product of the mutant allele. The increase in the freq uency of chromosome breaks probably resulted from p53wt inactivation, whereas changes in chromosome number might be induced by some addition al activities of p53 determined by mutations. Possible mechanisms for inducing heteroploidy by mutant p53 variants, including the role of en doreduplication in inducing hyper- and polyploidy, are discussed.