Mutation rates and mutational spectra in tumorigenic cell lines

The rate and molecular nature of spontaneous mutations at the hgprt locus were examined in a series of tumorigenic and non-tumorigenic closely related Chinese hamster fibroblastic (CHEF) cell lines. Mutation rates of tumorigenic cells determined by fluctuation analysis were found to range from the low rate also seen in non-tumorigenic cells to values increased up to 25-fold. No simple correlation was found between elevated mutation rates and tumorigenic potential. The nature of the mutational event was examined in a set of 136 thioguanine resistant mutants selected from several tumorigenic and non-tumorigenic CHEF lines. Significantly different frequencies of point mutations were found compared with large partial or whole gene deletions in different cell lines. The clonal inheritance of specific mutational patterns as well as the high frequencies of large deletions were novel findings. Hypotheses to explain these results are discussed in relation to the known genomic instability of tumour cells. I am honoured by the opportunity to contribute to this collection of papers dedicated to Professor Guido Pontecorvo on the occasion of his eightieth birthday. For almost half of this time I have been privileged to enjoy his friendship, and to benefit from his influence at critical stages in my scientific development.