Bryant P E, Iliakis G
Nucleic Acids Symp Ser. 1984(13):291-308.
To gain information about the possible pathway from primary DNA damage to cell killing via the formation of chromosome aberrations, we have examined the effects of the DNA synthesis inhibitor ara A on survival, on the occurrence of chromosome abnormalities and on the repair of DNA strand breaks. Our results are not inconsistent with the idea that the increased expression or 'fixation' of PLD measured after treatment with ara A is a reflection of an increase in the formation of chromosome damage comprising both exchange type and deletion type aberrations. These aberrations may arise from unrepaired or misrepaired dsb in the DNA. Treatment of irradiated cells with ara A results in a larger number of residual dsb which may be partly the reason for the increase in the frequency of acentric chromosome fragments. The reasons for the increase also in the frequency of exchange aberrations in the presence of ara A are not known but one possibility is that the probability of interaction between two dsb remains high during treatment with ara A due to the strong inhibition of dsb repair, whereas in untreated controls this probability decreases steeply with time after irradiation.
