<http://purl.org/dc/terms/description>
"DNA damage produced in C3H/HeN murine tissues by ionizing radiation was characterized at the level of\r\nthe individual cell with the goal of defining tissue dependent differences in DNA single-strand break (SSB)\r\ninduction and repair. Subsequently, nicotinamide, was examined as a modifier of initial DNA damage and\r\nSSB rejoining following irradiation. The alkaline comet assay, a single-cell gel electrophoresis method, was\r\nused to examine cells from SCCVM tumours, spleen, bone marrow, liver, jejunum, testis, thymus and\r\ncerebellum. Cells from all tissues irradiated in vitro showed similar radiosensitivity. However, for in vivo\r\nirradiation, rapid SSB rejoining which occurs in cells during irradiation led to differences between tissues.\r\nAlso, tumour and testis showed less damage in vivo than other normal tissues. Consistent with previous\r\nstudies, these two tissues were found to contain radiobiologically hypoxic cells. Efficiency of SSB rejoining\r\nwas cell type-dependent; cells from SCCVII tumors rejoined breaks about 5 times more rapidly than cells\r\nfrom cerebellum. Heterogeneity in speed of rejoining was minimal among cells of a tissue, and no\r\nsignificant damage remained 4 hours following 15 Gy. However, extensive DNA degradation was observed\r\nin all tissues except brain 48 hours after 15 Gy. DNA ladder patterns in agarose gels, typical of apoptosis,\r\nwere observed 4 hours after 2-10 Gy in spleen and thymus.\r\nThe vitamin B analogue, nicotinamide, was shown to improve testis and tumour oxygenation, in agreement\r\nwith other studies. A new observation was that nicotinamide (500 mg/kg or more) given before irradiation\r\ninhibited SSB rejoining in cells of all tissues except brain. Furthermore, radiation-induced DNA degradation\r\nwas found to be greatly accelerated by nicotinamide. Both effects are likely to involve poly(ADP-ribose)\r\npolymerase inhibition. However, while nicotinamide significantly retarded radiation-induced SSB rejoining\r\nin tumors, the biological significance of this effect is questionable since nicotinamide did not enhance\r\noxygen-independent killing of irradiated tumor cells."@en
<https://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0087188>