Enhancement of the rate of spontaneous mutation to 6-thioguanine resistance in mammalian cells by polyamine depletion.

Several lines of evidence have suggested, but not proved, that polyamines are associated with DNA in intact cells. In an attempt to investigate the roles of polyamines in gene-associated functions, we examined the effects of polyamine depletion on the spontaneous mutation rate in a rat basophilic leukemia cell line. The frequency of 6-thioguanine-resistant mutant cells increased by approximately 9-fold as a result of the treatment with alpha-difluoromethylornithine, a potent inhibitor of ornithine decarboxylase (EC 4.1.1.17). This increase was prevented by supplementing the cultures with putrescine, suggesting that polyamine depletion, but not the direct mutagenic action of the enzyme inhibitor, is responsible for the mutant-increasing effect. These results suggest that polyamines may participate in the conservation of genetic information at either the chromosome or gene level.