ABSTRACT
Cytotoxicity, extent of DNA double-strand breaks, and stimulation of poly(adenosine diphosphoribose)-synthesis were measured in two established human head and neck squamous carcinoma cell lines (183A and 1483) following x-irradiation. The 1483 cell line was 15-fold more resistant to x-ray-mediated cytotoxicity than was the 183A cell line. X-ray-mediated DNA strand cleavage also differed in these two cell lines with the absolute frequency of DNA double-strand breaks in the sensitive cells 183A cells being twice that in the resistant 1483 cell line. No detectable stimulation of poly(adenosine diphosphoribose)-synthesis was measured in the sensitive 183A cells whereas a marked increase in incorporation of [3H]-nicotinamide adenine dinucleotide was readily detected following x-irradiation of the resistant 1483 cells. These findings suggest a possible role of altered poly(adenosine diphosphoribose)-synthesis in the sensitivity of human head and neck squamous carcinoma cells to ionizing radiation.
Subject(s)
Cell Survival/radiation effects , DNA Damage , Nucleoside Diphosphate Sugars/radiation effects , Poly Adenosine Diphosphate Ribose/radiation effects , Carcinoma, Squamous Cell , Cell Division/radiation effects , Dose-Response Relationship, Radiation , Head and Neck Neoplasms , Humans , Poly Adenosine Diphosphate Ribose/biosynthesis , X-RaysABSTRACT
The inhibitors of poly(ADP-ribose) polymerase did not exert a radiomodifying effect on thymocytes. The inhibitors did not also influence single-strand breaks repair in DNA of nucleoids of irradiated cells. The participation of poly(ADP-ribosylation) system in increasing the availability of thymocyte DNA damages for repair enzymes was hardly probable since benzamide in these cells did not influence the level of spontaneous genome lesions recognized by endonucleases. A possible role of protein poly(ADP-ribosylation) in thymocyte DNA repair is discussed.
Subject(s)
Lymphocytes/radiation effects , Nucleoside Diphosphate Sugars/radiation effects , Poly Adenosine Diphosphate Ribose/radiation effects , Proteins/radiation effects , Radiation Tolerance , Thymus Gland/radiation effects , Animals , Cell Survival/drug effects , Cell Survival/radiation effects , DNA Damage , DNA Repair/drug effects , DNA Repair/radiation effects , DNA, Single-Stranded/drug effects , DNA, Single-Stranded/radiation effects , Gamma Rays , Lymphocytes/drug effects , Lymphocytes/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Poly(ADP-ribose) Polymerase Inhibitors , Thymus Gland/drug effects , Thymus Gland/metabolismABSTRACT
Exposure of human fibroblasts to 5 J/m2 of UV light resulted in a rapid increase of up to 1500% in the intracellular content of poly(ADP-ribose) and a rapid depletion of its metabolic precursor, NAD. When added just prior to UV treatment, the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, totally blocked both the increase of poly(ADP-ribose) and decrease in NAD for up to 2.5 h. Addition of 3-aminobenzamide at the time of maximal accumulation of poly(ADP-ribose) resulted in a decrease to basal levels with a half-life of approximately 6 min. The rates of accumulation of poly(ADP-ribose) and depletion of NAD were increased in the presence of either 1-beta-arabinofuranosylcytosine or hydroxyurea. Since these agents are known to cause an additional accumulation of DNA strand breaks following UV irradiation, these data provide evidence for a mechanism in which the rate of poly(ADP-ribose) synthesis following DNA damage is regulated in intact cells by the number of DNA strand breaks. Under conditions in which the synthesis of poly(ADP-ribose) was blocked, DNA repair replication induced by UV light was neither stimulated nor inhibited.
