RATE AND EXTENT OF DNA-REPAIR IN NONDIVIDING HUMAN-DIPLOID FIBROBLASTS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (3) , 819-825
Abstract
Rates of DNA repair in UV (254 nm)-irradiated nondividing human diploid fibroblasts were determined at doses as low as 1 J/m2 using an enzymatic assay for pyrimidine dimers. In normal cells, initial rates (dimers removed per 24 h) increased with dose to 20 J/m2 with no further increase at 40 J/m2 or less, repair occurred continuously over long post UV periods until all the damage that could be detected was removed (for 10 J/m2, this required 20 days; sensitivity of the assay was .apprx. 0.1 dimer/108 daltons). The overall rate curves appear as the sum of 2 1st-order reactions with different rate constants (rapid, 1.7 dimers/108 daltons/day; slow, 0.25 dimer/108 daltons/day). The slow reaction extrapolates to 30-40% of the original dimers. Populations irradiated a 2nd time after > 90% of the original damage was removed repaired the newly added DNA damage with similar kinetics and to the same extent. Repair kinetics in a xeroderma pigmentosum strain (XP12BE, complementation group A, 1 J/m2) lacks the rapid component and approximates the slow component of normal cells. If the slow component of normal cells is due to repair of less accessible dimers, then by analogy, slow excision repair in XP12BE may be due to the poor accessibility of all dimers. The XP12BE excision repair defect apparently is in the enzymes that render dimers in chromatin accessible to repair. [A determination of the kinetics of DNA repair and of the factors that control these kinetics in human cells is important to an eventual understanding of the relationship between carcinogen-induced DNA damage, its repair and carcinogenesis.].

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