Chemical Radiosensitization Studies With Mammalian Cells Growing In Vitro

Chapman, J. D.; Dugle, D.L.; Reuvers, A. P.; Gillespie, C.J.; Borsa, J.

doi:10.1016/b978-0-12-523350-7.50073-0

Cited by 34 publications

(17 citation statements)

References 31 publications

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“…32 for a fuller discussion). This equation has been shown to describe accurately the survival of Chinese hamster fibroblasts at all stages of the cell cycle (33), and in exponential growth with or without a variety of radiosensitizing and protecting agents (34). It follows from the model that unrepaired DSBs in the same cells are given by…”

Section: Possible Biological Significancementioning

confidence: 93%

DNA strand breaks, repair, and survival in x-irradiated mammalian cells.

Dugle¹,

Gillespie²,

Chapman³

1976

Proc. Natl. Acad. Sci. U.S.A.

134

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The yields of unrepairable single-and double-strand breaks in the DNA of x-irradiated Chinese hamster cells were measured by low-speed neutral and alkaline sucrose density gradient sedimentation in order to investigate the relation between these lesions and reproductive death. After maximal single-strand rejoining, at alldoses, the number of residual single-strand breaks was twice the number of residual double-strand breaks. Both double-strand and unrepairable single-strand breaks were proportional to the square of absorbed dose, in the range 10-50 krad. No (6, 8, 20-22, 25, 26).The technical difficulties inherent in measurements of SSBs and, particularly, DSBs in mammalian DNA, using velocity sedimentation, have been to some degree resolved by many recent studies (e.g., refs. 11, 21, and 22 The sedimentation velocity relation for determining DNA molecular weight was calibrated using intact strands of Bacillus subtilis bacteriophage SP50 DNA (duplex molecular weight 108). DNA strand breaks were quantified using a computer simulation of random breakage (27) applied to the molecular weight distributions from control samples (irradiated to 10.8 krad and incubated, see below). RESULTS AND DISCUSSIONAbsence of double-strand rejoining Three pairs of sedimentation profiles are shown in Fig. 1; each pair consists of profiles from an alkaline and a neutral gradient sedimentation of cells scraped from the same dish. The three pairs are controls (see below), cells irradiated to 54 krad and held at 00 until lysis, and cells incubated for 210 min at 370 after 54 krad. The latter case represents a separate experiment, shown here for convenient comparison, which is possible because the positions of the profiles are reproducible between experiments. The lines shown are the best fit, to profiles for irradiated cells, from computer simulation of random breakage applied to control DNA (27). The close agreement between lines and data points indicates that profiles for irradiated cells correspond to random breakage products. That is, both single-and double-strand breakage, and single-strand rejoining appear to be random (28).The profiles from irradiated cells show that, although 95% of the single-strand breaks were repaired, neither the number nor the distribution of double-strand breaks was significantly different after incubation. Nature of unrepairable single-strand breaks In the above experiment, centrifugation times were such that molecular weights from the neutral and alkaline gradients were closely in two to one correspondence for any sedimentation distance in the central region of the gradients (see upper and lower scales, Fig. 1). It is thus evident that the single-strand profile from incubated cells corresponds accurately to halves of the double-strand fragments from either incubated or unincubated cells. This observation was confirmed by a more detailed comparison. Thus, after incuba-809

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Section: Possible Biological Significancementioning

confidence: 93%

DNA strand breaks, repair, and survival in x-irradiated mammalian cells.

Dugle¹,

Gillespie²,

Chapman³

1976

Proc. Natl. Acad. Sci. U.S.A.

134

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“…Several studies have pointed out the efficiency of dimethylsulfoxide (DMSO) as an effective radioprotector by its ability to scavenge OH radicals. The protection does not increase at concentrations above 1 M (Chapman et al, 1975). This saturation allows us to define the indirect and direct effects as scavengeable or non-scavengeable, respectively (Ward, 1991).…”

confidence: 99%

Effect of DMSO on radiation-induced chromosome aberrations analysed by FISH

Cigarrán

Barrios²,

Caballı́n³

et al. 2004

Cytogenet Genome Res

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The purpose of the present work was to determine if the described reduction in the frequency of radiation-induced chromosome aberrations by DMSO is homogeneous within different human chromosomes. Blood samples were irradiated with 4 Gy of X-rays in absence and presence of 0.5 M DMSO. FISH painting was carried out independently for human chromosomes 1, 2, 3, 4, 7, 11 and 12. The observed frequencies of apparently simple translocations and dicentrics for all these chromosomes, showed a homogeneous reduction when the irradiation was done in the presence of DMSO. Moreover, a better fit between the observed and expected frequencies was obtained when (DNA content)^2/3 was used to calculate the expected frequencies, instead of just the DNA content. This result supports the idea that for exchange type aberrations, a better adjustment is obtained when the surface area of spherical chromosome territories is considered.

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“…Attention has focused on its ability to sensitize hypoxic cells to the effects of sparsely ionizing radiations, and it is on this basis and in this context that its clinical use is being actively pursued at the present time (Denekamp and Harris, 1975;Sheldon, Foster and Fowler, 1974;Gray et al, 1976;Brown, 1975;Chapman et al, 1975).…”

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confidence: 99%