Effects of Daunomycin and Radiation on Cell-survival and Repair of DNA Single-strand Breaks

Abstract

The combined action of Daunomycin and irradiation was investigated using mouse L-929 cells in culture. Survival of cells was measured with the colony assay. Sedimentation in alkaline sucrose gradients was used to study repair of DNA single-strand breaks (SSB) in the presence of various concentrations of Daunomycin. A small increase in radio-sensitivity, as measured by decreasing Do, was obtained for doses of Daunomycin that are considerably toxic to the cells (0.1 microgram/ml). However, the Dq values remained constant even at high concentrations indicating that Daunomycin does not interfere with recovery processes. The rate of rejoining of SSB remained constant up to 1.0 microgram/ml, whereas concentrations of Daunomycin as high as 10 microgram/ml reduced the velocity of repair by a factor of 13. Our data show that concentrations of Daunomycin similar to those required for other DNA-binding drugs are required to inhibit SSB repair. For clinical purposes, no increase in tumour-killing efficiency may be expected from a combined treatment with Daunomycin and radiation.

Comparative study of the repair kinetics of chromosomal aberrations and DNA strand breaks in proliferating and quiescent

“…The fast tim e constant s 1 » 4 m in, m easured in quiescent and proliferating cells with this technique, agrees with time constants published for single-strand break repair processes ranging between 3 and 15 m in (e.g. Ahnstro È m and Edvardson 1974, Ben-H ur and Elkind 1974, Roots and Sm ith 1975, Baisch et al 1977, Bryant and Blo È cher 1980, van der Schaans et al 1989, Boerrigter and Vijg 1992. This tim e constant is therefore associated with single-strand break repair.…”

“…W ith m ethods recording singleas well as double-strand breaks, two or even m ore processes have been identi® ed, with a`fast' tim e constant ranging from 3 to 10 min, which is thought to represent single-stran d break repair (e.g. Ahnstro È m and Edvardson 1974, Ben -H ur an d E lkind 1974, Baisch et al 1977, Bryan t and B lo È cher 1980, van der Schaans et al 1989, Boerrigter and Vijg 1992, as well as`interm ediat e' an d`slow' tim e constants, ranging from som e m inutes to several hours, probably re¯ecting double-stran d break repair and other repair m ech anism s (Bryant and Blo È cher 1980, Weibezahn et al 1985, D ikom ey and Franzke 1986a, Iliakis et al 1987, O live et al 1991.…”

Three Classes of DNA Strand Breaks Induced by X-irradiation and Internal β-rays

“…Fast, slow and non-repaired strand breaks were considered. For fast repaired strand breaks, which represent the majority after X-irradiation and which are all assumed to be single-strand breaks, repair half-times () ranging from 2 to 10min have been reported ( Edvardsson 1974, Ben Hur andElkind 1974, Dugle and Gillespie 1975, Koch and Painter 1975, Roots and Smith 1975, Dugle et al 1976, Baisch et al 1977, Bryant and Blocher 1980, Dikomey 1982, van der Schans et al 1983). The half-times of slowly repaired trand breaks, which are considered to be double-strand breaks, are generally found in the range of T= 50-300min (Furuno et al 1979, Bryant and B16ocher 1980, B16cher and Pohlit 1982, Dikomey 1982.…”