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Title: THE EFFECT OF 5-HALOGENATED DEOXYURIDINES ON THE FREQUENCY OF X-RAY-INDUCED CHROMOSOMAL ABERRATIONS IN VICIA FABA

Journal Article · · Hereditas (Sweden)

The effects of 5-fluorodeoxyaridine (FUdR) and the thymidine analogs 5- chlorodeoxyuridine (CUdR), 5-bromodeoxyuridine (BUdR), and 5-iododeoxyuridine (IUdR) on the frequency of x-ray-induced chromatid aberrations in the root tips were studied. Pretreatments with CUdR, BUdR, and IUdR at concentrations of 100 mu M increased the effect of a given dose of x rays by factors of 1.3, 1.6, and 1.9, respectively. IUdR increased the frequency of x-rayinduced aberrations to the same extent whether the roots were irradiated under anaerobic or aerobic conditions. For maximum enhancement, it was necessary to treat the roots for at least 24 hr with the thymidine analogs. Posttreatment with IUdR did not influence radiosensitivity. When x irradiation was combined with a FUdR treatment, and the effect was scored in anaphase, the number of fragments was markedly increased and the number of bridges was decreased, in comparison with the x-ray control. The FUdR treatment was equally effective when given after as when given before and during irradiation. The results show that the frequency of x-ray-induced chromatid aberrations in the root tips of Vicia is influenced in the same way by these 5-halogenated deoxyaridines as is the killing effect of x rays on mammalian cells in tissue culture and on bacteria. When the thynridine analogs were tested in equlmolar concentrations in Vicia IUdR was the most effective and CUdR the least effective. The difference in effectivity could be a result of a different incorporation of the analogs into DNA. The fact that a 4- hr pretreatment with IUdR resulted in an increased frequency of aberrations only when the roots were fixed between 9 and 15 hr after irradiation indicates that only those cells which were undergoing DNA synthesis when exposed to IUdR were sensitized. This is consistent with the idea that incorporation of thymidine and its analogs can reverse or prevent the chromosome damage produced by the deoxyuridine analog FUdR is consistent with the idea that the effect of FUdR on chromosome structure is a result of its inhibitory effect on the synthesis of thymidylic acid. The experiments have further shown that whereas FUdR-induced thymidine deficiency produces fragmentation of chromosomes, the incorporation of thymidine analogs, such as CUdR, BUdR, and IUdR, into chromosomal DNA does not itself, as a rue, cause chromosomal aberrations, but it makes the chromosomes more sensitive to the chromosome-breaking effect of x rays. It is concluded that the stability of the chromosome is dependent on the composition and state of its DNA, favoring a hypothesis of chromosome organization which allots to DNA an important fanction in keeping the chromosomes intact. (BBB)

Research Organization:
Uppsala Univ. (Sweden)
Sponsoring Organization:
USDOE
NSA Number:
NSA-18-011730
OSTI ID:
4121732
Journal Information:
Hereditas (Sweden), Vol. Vol: 49; Other Information: Orig. Receipt Date: 31-DEC-64
Country of Publication:
Country unknown/Code not available
Language:
English