Increased gene amplification in L5178Y mouse lymphoma cells with hydroxyurea-induced chromosomal aberrations

Chromosomal aberrations and dihydrofolate reductase gene amplification are observed in L5178Y mouse lymphoma cells after treatment with hydroxyurea. The types of aberrations include polyploidy, endoreduplication, chromosome fragmentation, and the presence of extrachromosomal DNA. Hydroxyurea-treated cells analyzed by cell sorting showed a subpopulation of cells with increased DNA and increased dihydrofolate reductase. This subpopulation shows a high incidence of chromosome aberrations and an increased frequency of dihydrofolate reductase gene amplification. Hydroxyurea-treated cells with the normal amount of DNA and dihydrofolate reductase have few aberrations and a low frequency of dihydrofolate reductase gene amplification. We propose that hydroxyurea treatment causes overreplication of DNA and that recombination of overreplicated DNA can lead to chromosome aberrations and gene amplification.