Diphtheria toxin resistance in human fibroblast cell strains from normal and cancer-prone individuals

Mutants resistant to diphtheria toxin (Dipr) have been selected from a variety of human fibroblast cell strains derived from both normal subjects and individuals with known genetic predisposition to cancer such as xeroderma pigmentosum, Fanconi anemia and Bloom's syndrome. Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) led to a marked increase in the frequency of Dipr mutants in various cell strains. The increase in the frequency of Dipr mutants occurred in a linear dose-dependent manner in response to MNNG and ethyl methanesulfonate, in one of the cell strains examined. The rate of mutation to diphtheria toxin as determined by fluctuation analysis was very similar in various cell strains (1-3 x 10(-7) mutations/cell/generation), except for the strain GM1492 (8.8 x 10(-7) mutations/cell/generation) which is derived from a Bloom syndrome patient.