Chromosome Damage Induced by 5-Fluoro-2′ -Deoxyuridine in Relation to the Cell Cycle of the Chinese Hamster

Summary

Chromosome damage is induced by 5-fluoro-2′-deoxyuridine (FUDR) in Chinese hamster fibroblast line Don and clone strain Don-C during the DNA synthesis period. The G₂ period is insensitive. The characteristic shattering of chromosomes is induced in FUDR-blocked cells at the beginning of the S period with a very narrow time span (3 ± 0.5 hrs after metaphase). Only the early replicating sites or euchromatin of the chromosomes is affected. The Y and the long arm of the × remain unbroken. This period is the most sensitive stage to damage and many cells do not reach metaphase. Cells treated in the later part of the S period are not blocked by FUDR. They show a low frequency of open chromosome breaks in the late or heterochromatic regions. These cells are blocked at the beginning stage of the next S phase. When released by nonradioactive thymidine (TDR), they come to mitosis with one chromatid labeled. The results indicate a large enough TDR pool to permit cells in the mid-S phase to complete DNA synthesis without relying on the endogenous pathway. This TDR pool can be demonstrated by pulse labeling synchronized G₁ cells for autoradiography. When such cells are fixed with formaldehyde, the nuclei of the G₁ cells are labeled. However, acid fixation removes the label.