Number Of DNA Single-strand Breaks Research Articles

Spontaneous cancer and its possible relationship to oxygen metabolism.

Mortality statistics for cancer in various countries and periods of time indicate that there has been little effect of industrialization on the inherent or spontaneous rate of occurrence of cancer. From U.S. cancer statistics and the BEIR values [Report of the Advisory Committee on the Biological Effects of Ionizing Radiation (1979)] for radiation dose response, the ionizing radiation exposure required to produce a number of cancers equal to this spontaneous incidence was estimated to lie between 450 and 2100 rads (1 rad = 0.01 J/kg). From these "cancer equivalent" doses the number of single-strand DNA breaks required to produce the spontaneous cancers is estimated to be 0.26-1.3 per cell DNA per day. It is suggested that the univalent reduction of oxygen in normal metabolism to O2- and subsequent production of more harmful radicals is the source of the DNA defects that, in cases where the defense mechanisms fail, lead to spontaneous cancer in the individual.

Effect of hyperthermia on DNA single-strand breaks induced by bleomycin in Hela cells.

The effect of hyperthermia (43 approximately 45 degrees) on DNA single-strand breaks induced by bleomycin was examined in HeLa cells by the alkaline sucrose gradient sedimentation analysis. When HeLa cells were exposed to a temperature of 43 degrees approximately 45 degrees for 1 hr, only a small number of DNA single-strand breaks than bleomycin treatment at 37 degrees. The DNA strand breaks induced by bleomycin were almost completely repaired by post-treatment incubation of the cells in the control medium at 37 degrees. On the contrary, the repairing capacity of the cells was markedly inhibited by post-treatment incubation at 43 degrees, and this inhibition of cell repair seemed irreversible because no repair was found after an additional incubation of the cells at 37 degrees for 1 hr. These results support the possibility that the mechanism of synergism between the effect of bleomycin and hyperthermia may be related to the inhibition of DNA repair.

Cytotoxicity and DNA damage to mammalian cells by nitrofurans

Nitrofurazone, nitrofurantoin, furazolidone, furaltadone and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) were toxic to cultured mouse L cells. The extent of toxicity and the rate of reduction of nitrofurazone increased markedly as the oxygen content of the incubation medium was lowered. The toxic effect of nitrofurans was decreased by addition of serum and was much greater in phosphate-buffered saline containing glucose (PSG) than in medium. Damage to L cell DNA by nitrofurans increased as the oxygen concentration decreased from 21% to 0%. The concentration of nitrofurazone and duration of exposure also determined the number of DNA single-strand breaks. It is suggested that toxicity and DNA damage may result from the actions of toxic intermediates in the metabolic reduction of nitrofurans.